PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
18988309-7	2008	RESULTS: Mechanical thresholds decreased significantly and serum IL-6 level increased significantly after operation in Group 2 compared with control (P<0.01), and these changes were reversed respectively by tramadol in a dose-dependent manner (P<0.05 and P<0.01, respectively).	Tramadol	210-218	interleukin 6	Rattus norvegicus	65-69
18640130-0	2008	Modelling the pharmacokinetics of tramadol: on the difference between CYP2D6 extensive and poor metabolizers.	Tramadol	34-42	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	70-76
18640130-8	2008	A difference in metabolization rate between CYP2D6 poor and extensive metabolizers is also found, and the stereoselectivity in the O-demethylation of tramadol highlighted.	Tramadol	150-158	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	44-50
18713907-0	2008	Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication.	Tramadol	28-36	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	76-82
18758760-3	2008	Furthermore, we found that the subcutaneous (s.c.) injection of tramadol and M1 each produced a significant place preference in mice, and these effects were significantly suppressed by pretreatment with the MOR antagonist beta-funaltrexamine.	Tramadol	64-72	opioid receptor, mu 1	Mus musculus	207-210
18758760-8	2008	DISCUSSION: Our present data support the notion that the rewarding effect induced by tramadol is mediated mainly through metabolism to its active metabolite M1 via MOR.	Tramadol	85-93	opioid receptor, mu 1	Mus musculus	164-167
18713907-4	2008	Analysis of the patient"s genotype revealed a CYP2D6 gene duplication resulting in ultra-rapid metabolism of tramadol to its active metabolite (+)O-desmethyltramadol.	Tramadol	109-117	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	46-52
18713907-6	2008	This genetic CYP2D6 variant is particularly common in specific ethnic populations and should be a future diagnostic target whenever administration of tramadol or codeine is anticipated, as both drugs are subject to a comparable CYP2D6-dependent metabolism.	Tramadol	150-158	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	13-19
18713907-6	2008	This genetic CYP2D6 variant is particularly common in specific ethnic populations and should be a future diagnostic target whenever administration of tramadol or codeine is anticipated, as both drugs are subject to a comparable CYP2D6-dependent metabolism.	Tramadol	150-158	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	228-234
18520597-1	2008	Several studies have demonstrated the impact of CYP2D6 polymorphism on the pharmacokinetics of tramadol.	Tramadol	95-103	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	48-54
18317231-0	2008	Postmenstrual age and CYP2D6 polymorphisms determine tramadol o-demethylation in critically ill neonates and infants.	Tramadol	53-61	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	22-28
18597654-6	2008	Cytochrome P450 (CYP) 2D6 mutations influence the analgesic effect of codeine and tramadol, and polymorphism of CYP2C9 is potentially linked to an increase in nonsteroidal anti-inflammatory drug-induced adverse events.	Tramadol	82-90	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-25
18499628-0	2008	The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1.	Tramadol	20-28	LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 1	Cricetulus griseus	56-96
18499628-3	2008	As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol.	Tramadol	263-271	LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 1	Cricetulus griseus	3-43
18499628-3	2008	As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol.	Tramadol	263-271	LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 1	Cricetulus griseus	45-50
18499628-3	2008	As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol.	Tramadol	263-271	LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 1	Cricetulus griseus	219-224
18499628-6	2008	CONCLUSIONS: Collectively, these findings strongly support the intriguing and novel concept that tramadol acts as an agonist of TRPV1.	Tramadol	97-105	LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 1	Cricetulus griseus	128-133
18499628-7	2008	Considering that activation of TRPV1 on sensory neurons is followed by a local release of vasoactive neuropeptides and a marked desensitization of the afferent fibers (hence termination of pain sensation), our findings may equally explain both the desired analgesic as well as the often-seen, yet "unexpected," local side effects (e.g., initiation of burning pain and erythema) of tramadol.	Tramadol	381-389	LOW QUALITY PROTEIN: transient receptor potential cation channel subfamily V member 1	Cricetulus griseus	31-36
18520597-2	2008	However, the relationship between the O-demethylation of tramadol and O-desmethyltramadol (M1) and CYP2D6 activity has not previously been investigated with tramadol in multimedicated outpatients under steady-state conditions.	Tramadol	57-65	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	99-105
18520597-2	2008	However, the relationship between the O-demethylation of tramadol and O-desmethyltramadol (M1) and CYP2D6 activity has not previously been investigated with tramadol in multimedicated outpatients under steady-state conditions.	Tramadol	81-89	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	99-105
18520597-12	2008	In conclusion, the impact of the CYP2D6 polymorphism on the pharmacokinetics of tramadol was clearly demonstrated in a group of multimedicated patients treated with tramadol under steady-state conditions.	Tramadol	80-88	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	33-39
18520597-12	2008	In conclusion, the impact of the CYP2D6 polymorphism on the pharmacokinetics of tramadol was clearly demonstrated in a group of multimedicated patients treated with tramadol under steady-state conditions.	Tramadol	165-173	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	33-39
18417104-6	2008	ketanserin (a 5-HT2A receptor antagonist) on tramadol analgesia was observed.	Tramadol	45-53	5-hydroxytryptamine receptor 2A	Rattus norvegicus	14-20
18417104-9	2008	Expression of the 5-HT2A receptor mRNA in NRM, ipsilateral vlPAG, and the ipsilateral spinal dorsal horn of arthritic rats was significantly increased after tramadol treatment.	Tramadol	157-165	5-hydroxytryptamine receptor 2A	Rattus norvegicus	18-24
18417104-10	2008	These results suggest that 5-HT2A receptors are involved in the analgesic effect of tramadol.	Tramadol	84-92	5-hydroxytryptamine receptor 2A	Rattus norvegicus	27-33
18234187-0	2008	Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor knock out mice brain.	Tramadol	29-37	adrenergic receptor, alpha 2b	Mus musculus	109-117
18417104-11	2008	This study provides evidence for involvement of 5-HT2A receptors in the tramadol analgesia of inflammatory pain.	Tramadol	72-80	5-hydroxytryptamine receptor 2A	Rattus norvegicus	48-54
18234187-10	2008	Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors.	Tramadol	55-63	adrenergic receptor, alpha 2b	Mus musculus	78-100
18234187-10	2008	Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors.	Tramadol	55-63	adrenergic receptor, alpha 2b	Mus musculus	159-167
18356636-6	2008	Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors.	Tramadol	0-8	prostaglandin-endoperoxide synthase 2	Homo sapiens	272-288
18356636-6	2008	Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors.	Tramadol	0-8	prostaglandin-endoperoxide synthase 2	Homo sapiens	290-295
18204346-0	2008	Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol.	Tramadol	87-95	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	15-21
18204346-1	2008	The analgesic drug tramadol is bioactivated by CYP2D6 to the opioid receptor agonist O-desmethyltramadol.	Tramadol	19-27	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	47-53
18204346-3	2008	However, the effects of the CYP2D6 duplication on kinetics and dynamics of tramadol have not been systematically studied.	Tramadol	75-83	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	28-34
19235528-5	2008	Both postmenstrual age and pharmacogenetics (CYP2D6) were covariates of tramadol metabolism in newborns.	Tramadol	72-80	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	45-51
17991273-0	2007	Codeine and tramadol analgesic efficacy and respiratory effects are influenced by CYP2D6 genotype.	Tramadol	12-20	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	82-88
17377112-10	2007	Conversely, a prevention of the increase in TNF-alpha levels was observed only in rats treated with nimesulide or tramadol and paracetamol in combination.	Tramadol	114-122	tumor necrosis factor	Rattus norvegicus	44-53
17976797-2	2007	Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism.	Tramadol	19-27	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
17976797-2	2007	Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism.	Tramadol	19-27	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	71-77
17976797-2	2007	Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism.	Tramadol	111-119	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
17976797-2	2007	Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism.	Tramadol	111-119	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	71-77
17361124-9	2007	In conclusion, CYP2D6 genotype determined concentrations of O-desmethyltramadol enantiomers and influenced efficacy of tramadol treatment.	Tramadol	71-79	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	15-21
17361124-0	2007	Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes.	Tramadol	18-26	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	76-82
17393145-2	2007	OBJECTIVES: The present study was undertaken to evaluate the potential role of 5-HT(1A) receptors and opioids receptors in the analgesic effect of tramadol in neuropathic pain.	Tramadol	147-155	5-hydroxytryptamine receptor 1A	Rattus norvegicus	79-86
17393145-7	2007	CONCLUSIONS: These findings suggest the involvement of opioid and 5-HT(1A) receptors in the antinociceptive effect of tramadol and support the idea that the combination of tramadol with compounds having 5-HT(1A) antagonist properties could be a new strategy to improve tramadol-induced analgesia in neuropathic pain.	Tramadol	118-126	5-hydroxytryptamine receptor 1A	Rattus norvegicus	66-73
17393145-7	2007	CONCLUSIONS: These findings suggest the involvement of opioid and 5-HT(1A) receptors in the antinociceptive effect of tramadol and support the idea that the combination of tramadol with compounds having 5-HT(1A) antagonist properties could be a new strategy to improve tramadol-induced analgesia in neuropathic pain.	Tramadol	118-126	5-hydroxytryptamine receptor 1A	Rattus norvegicus	203-210
17570739-0	2007	Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics.	Tramadol	41-49	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	10-16
17230457-2	2007	We report clinical and polysomnographic accounts of a patient developing RLS augmentation after long-term treatment with tramadol, an opioid agonist with selectivity for mu-receptor and added norepinephrine and serotonin reuptake inhibition properties.	Tramadol	121-129	RLS1	Homo sapiens	73-76
17230457-3	2007	Polysomnographic measures showed an improvement of RLS and a disappearance of diurnal sensory and motor RLS symptoms after tramadol was stopped.	Tramadol	123-131	RLS1	Homo sapiens	104-107
17230457-4	2007	Our case confirms a recent retrospective report of augmentation of RLS after treatment with tramadol, and begs the question whether augmentation is truly restricted to dopaminergic drugs.	Tramadol	92-100	RLS1	Homo sapiens	67-70
17175164-0	2007	Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites in relation to CYP2D6 phenotype.	Tramadol	20-28	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	97-103
17175164-1	2007	OBJECTIVE: Our objective was to evaluate the effect of CYP2D6 phenotype in the enantioselective metabolism of tramadol in Spanish healthy human volunteers.	Tramadol	110-118	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	55-61
17175164-5	2007	RESULTS: The plasma concentrations of both tramadol enantiomers were consistently higher in PMs than in EMs of CYP2D6, with 1.98- and 1.74-fold differences in the mean area under the plasma concentration-time curves (AUC), respectively.	Tramadol	43-51	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	111-117
17175164-11	2007	CONCLUSIONS: The polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol enantiomers.	Tramadol	95-103	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	29-35
18488071-4	2007	Tramadol, a mild opioid agonist and norepinephrine and serotonin reuptake inhibitor, is recommended by current guidelines for the treatment of moderate to moderately severe pain in patients who have not responded to previous oral therapy, or in patients who have contraindications to COX-2 inhibitors and nonselective NSAIDs.	Tramadol	0-8	prostaglandin-endoperoxide synthase 2	Homo sapiens	284-289
17265061-0	2007	Pharmacokinetics of tramadol is affected by MDR1 polymorphism C3435T.	Tramadol	20-28	ATP binding cassette subfamily B member 1	Homo sapiens	44-48
17570739-1	2007	BACKGROUND AND OBJECTIVE: Tramadol is metabolized by the highly polymorphic enzyme cytochrome P450 (CYP)2D6.	Tramadol	26-34	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	83-107
17570739-2	2007	Patients with different CYP2D6 genotypes may respond differently to tramadol in terms of pain relief and adverse events.	Tramadol	68-76	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	24-30
17570739-17	2007	CONCLUSION: CYP2D6 activity may play an important role in determining the pharmacokinetics of tramadol and in predicting its adverse effects.	Tramadol	94-102	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	12-18
16832657-0	2006	Differential role of 5-HT1A and 5-HT1B receptors on the antinociceptive and antidepressant effect of tramadol in mice.	Tramadol	101-109	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	21-38
16497087-0	2007	Miotic action of tramadol is determined by CYP2D6 genotype.	Tramadol	17-25	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	43-49
16497087-1	2007	Polymorphic CYP2D6 is the enzyme that activates the opioid analgesic tramadol by O-demethylation to its active metabolite O-demethyltramadol (M1).	Tramadol	69-77	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	12-18
16497087-2	2007	Our objective was to determine the opioid effects measured by pupillary response to tramadol of CYP2D6 genotyped volunteers in relation to the disposition of tramadol and M1 in plasma.	Tramadol	84-92	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	96-102
16497087-2	2007	Our objective was to determine the opioid effects measured by pupillary response to tramadol of CYP2D6 genotyped volunteers in relation to the disposition of tramadol and M1 in plasma.	Tramadol	158-166	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	96-102
16960721-0	2006	Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population.	Tramadol	60-68	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
16960721-2	2006	The aim of the present study was to investigate whether the CYP2D6*10 allele has an impact on the postoperative analgesia effect of tramadol in Chinese patients recovering from major abdominal surgery.	Tramadol	132-140	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
16960721-12	2006	CONCLUSIONS: This study indicates that the CYP2D6*10 allele has significant impact on analgesia with tramadol in a Chinese population.	Tramadol	101-109	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	43-49
16631290-5	2006	CYP2D6 metabolizes other opioid analgesics, including tramadol, dihydrocodeine, oxycodone and hydrocodone, although they have been less systematically studied.	Tramadol	54-62	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
17288152-1	2006	A novel technique of liquid phase microextraction supported by hollow fiber membrane (LPME-HFM) was applied to extract tramadol in tap water, urine and human plasma.	Tramadol	119-127	nuclear RNA export factor 1	Homo sapiens	131-134
17175820-0	2006	Attenuation of C-reactive protein increases after exodontia by tramadol and ibuprofen.	Tramadol	63-71	C-reactive protein	Homo sapiens	15-33
17175820-6	2006	At 72 hours, C-reactive protein had increased over postsurgery baseline by 123% in the tramadol group (P < .001), 84% in the ibuprofen group (P < .001), and only 37% in the combined analgesic group (P = .078).	Tramadol	87-95	C-reactive protein	Homo sapiens	13-31
16226908-4	2006	Tramadol suppressed the amplitude of delayed rectifier K(+) current (I(K(DR))) in a concentration-dependent manner with an IC(50) values of 25 microM.	Tramadol	0-8	kinase insert domain protein receptor	Mus musculus	71-76
16226908-5	2006	Tramadol (30 microM) also shifted the steady-state inactivation of I(K(DR)) to a more negative membrane potential by approximately -15 mV.	Tramadol	0-8	kinase insert domain protein receptor	Mus musculus	69-74
16226908-7	2006	Tramadol-induced block of I(K(DR)) observed in this study could be partly responsible for its anti-depressant action.	Tramadol	0-8	kinase insert domain protein receptor	Mus musculus	28-33
16832657-2	2006	OBJECTIVES: The present study was undertaken to evaluate the potential role of 5-HT1A and 5-HT1B receptors on the analgesic and antidepressant-like effect of tramadol.	Tramadol	158-166	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	79-96
16832657-6	2006	CONCLUSIONS: These findings suggest that 5-HT1A receptors modulate the analgesic and the antidepressant-like effects of tramadol in differing ways.	Tramadol	120-128	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	41-47
16832657-8	2006	In contrast, the 5-HT1A receptors located in the forebrain may be responsible for the blockade of the antidepressant-like effect of tramadol.	Tramadol	132-140	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	17-23
17120754-2	2006	We aimed to observe the effects of morphine, fentanyl and tramadol on NF-kappa B and IL-2 from both laboratory and clinical perspective.	Tramadol	58-66	nuclear factor kappa B subunit 1	Homo sapiens	70-80
29788657-5	2006	Thus, cytochrome P450 (CYP)2D6 polymorphism influences codeine and tramadol analgesic effects, CYP2C9 has an impact on the disposition of some nonsteroidal anti-inflammatory drugs, and opioid receptor polymorphism (118A>G) may reduce morphine potency.	Tramadol	67-75	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	6-30
16730359-6	2006	The inhibition of the synthesis of 5-HT by p-chlorophenylalanine and the pre-administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT at 40microg/kg, caused a significant potentiation of the tramadol effect decreasing the ED(50) by 53% and 67% respectively.	Tramadol	193-201	5-hydroxytryptamine receptor 1A	Homo sapiens	99-116
16427041-2	2006	The (+) and (-) enantiomers of tramadol suppressed the human 5-HT transporter concentration-dependently (IC50=1.0 and 0.8 microM, respectively), resulting in 97% and 87% transport inhibition at their respective initial plasma concentrations (9.5 microM).	Tramadol	31-39	solute carrier family 6 member 4	Homo sapiens	61-77
16427041-3	2006	The (+) and (-) enantiomers of the active tramadol metabolite were less potent than tramadol in inhibiting the human 5-HT transporter (IC50=15 and 44 microM, respectively), resulting in 19.2% and 4.8% transport inhibition at their highest plasma concentrations (2.5 microM).	Tramadol	42-50	solute carrier family 6 member 4	Homo sapiens	117-133
16427041-3	2006	The (+) and (-) enantiomers of the active tramadol metabolite were less potent than tramadol in inhibiting the human 5-HT transporter (IC50=15 and 44 microM, respectively), resulting in 19.2% and 4.8% transport inhibition at their highest plasma concentrations (2.5 microM).	Tramadol	84-92	solute carrier family 6 member 4	Homo sapiens	117-133
16427041-6	2006	In conclusion, at clinical plasma concentrations tramadol potently suppresses the human 5-HT transporter, whereas it has only a slight effect on the human 5-HT3A receptor.	Tramadol	49-57	solute carrier family 6 member 4	Homo sapiens	88-104
16763825-0	2006	Enantioselective pharmacokinetics of tramadol in CYP2D6 extensive and poor metabolizers.	Tramadol	37-45	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	49-55
16763825-1	2006	OBJECTIVE: To describe in detail the intravenous, single oral and multiple oral dose enantioselective pharmacokinetics of tramadol in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs).	Tramadol	122-130	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	134-140
16763825-9	2006	CONCLUSION: The impact of CYP2D6 phenotype on tramadol pharmacokinetics was similar after single oral, multiple oral and intravenous administration displaying significant pharmacokinetic differences between EMs and PMs of (+)-tramadol, (-)-tramadol, -(+)-M1 and (-)-M1.	Tramadol	46-54	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	26-32
16763825-9	2006	CONCLUSION: The impact of CYP2D6 phenotype on tramadol pharmacokinetics was similar after single oral, multiple oral and intravenous administration displaying significant pharmacokinetic differences between EMs and PMs of (+)-tramadol, (-)-tramadol, -(+)-M1 and (-)-M1.	Tramadol	222-234	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	26-32
16763825-9	2006	CONCLUSION: The impact of CYP2D6 phenotype on tramadol pharmacokinetics was similar after single oral, multiple oral and intravenous administration displaying significant pharmacokinetic differences between EMs and PMs of (+)-tramadol, (-)-tramadol, -(+)-M1 and (-)-M1.	Tramadol	237-248	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	26-32
16763825-10	2006	The O-demethylation of tramadol was catalysed stereospecific by CYP2D6 in the way that very little (+)-M1 was produced in PMs.	Tramadol	23-31	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	64-70
16368820-0	2006	The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6.	Tramadol	24-32	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	98-104
16368820-1	2006	Tramadol analgesia results from a monoaminergic effect by tramadol itself and an opioid effect of its metabolite (+)-M1 formed by O-demethylation of tramadol by CYP2D6.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	161-167
16368820-1	2006	Tramadol analgesia results from a monoaminergic effect by tramadol itself and an opioid effect of its metabolite (+)-M1 formed by O-demethylation of tramadol by CYP2D6.	Tramadol	149-157	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	161-167
17401159-0	2006	Effects of prolonged treatment with the opiate tramadol on prodynorphin gene expression in rat CNS.	Tramadol	47-55	prodynorphin	Rattus norvegicus	59-71
17401159-2	2006	In this paper, we evaluated the effects of the repeated administration (7 d) of different doses of tramadol (10, 20, and 80 mg/kg, intraperitoneally) on the opioid precursor prodynorphin biosynthesis, in comparison with morphine (10 mg/kg, intraperitoneally), in the rat central nervous system (CNS).	Tramadol	99-107	prodynorphin	Rattus norvegicus	174-186
17401159-5	2006	The highest dose of tramadol (80 mg/kg) decreased prodynorphin mRNA levels in the hypothalamus and the hippocampus but not in the striatum.	Tramadol	20-28	prodynorphin	Rattus norvegicus	50-62
17401159-7	2006	They indicate that the alterations of prodynorphin gene expression caused by tramadol and morphine show a different pattern that may be related to the different abuse potential of the two analgesic drugs.	Tramadol	77-85	prodynorphin	Rattus norvegicus	38-50
17120754-2	2006	We aimed to observe the effects of morphine, fentanyl and tramadol on NF-kappa B and IL-2 from both laboratory and clinical perspective.	Tramadol	58-66	interleukin 2	Homo sapiens	85-89
15961977-0	2005	Tramadol as a new probe for cytochrome P450 2D6 phenotyping: a population study.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	28-47
16140165-1	2005	Clinical observation found that tramadol, mu opioid receptor (MOR) agonist and serotonin (5-HT) reuptake inhibitor, has a hypoglycemic effect in type 2 diabetes patients.	Tramadol	32-40	opioid receptor mu 1	Homo sapiens	42-60
16140165-1	2005	Clinical observation found that tramadol, mu opioid receptor (MOR) agonist and serotonin (5-HT) reuptake inhibitor, has a hypoglycemic effect in type 2 diabetes patients.	Tramadol	32-40	opioid receptor mu 1	Homo sapiens	62-65
16140165-3	2005	This study showed that tramadol activated a neuronal insulin signaling cascade by increasing the induction of insulin receptor substrate-2 expression in primary cultured neuronal cells while this activation was suppressed by naloxone (MOR inhibitor) and dexamethasone (non-specific inhibitor of MOR and 5-HT receptor, DEX).	Tramadol	23-31	opioid receptor mu 1	Homo sapiens	235-238
16140165-3	2005	This study showed that tramadol activated a neuronal insulin signaling cascade by increasing the induction of insulin receptor substrate-2 expression in primary cultured neuronal cells while this activation was suppressed by naloxone (MOR inhibitor) and dexamethasone (non-specific inhibitor of MOR and 5-HT receptor, DEX).	Tramadol	23-31	opioid receptor mu 1	Homo sapiens	295-298
16140165-4	2005	Glucose utilization of the cerebral cortex and hypothalamus was enhanced by a 4-week-tramadol administration in 90% pancreatectomized rats, in vivo, as assessed by measurement of glucokinase expression and glycogen deposition via activating insulin signaling cascade such as neuronal cells in vitro.	Tramadol	85-93	glucokinase	Rattus norvegicus	179-190
16140165-8	2005	The data suggest that tramadol ameliorates peripheral glucose metabolism through central activation of MOR, and that central and peripheral glucose metabolism are therefore likely to be interrelated.	Tramadol	22-30	opioid receptor mu 1	Homo sapiens	103-106
16129989-5	2005	Cytochrome P-450 2D6 slow metabolizers derived greater analgesia from tramadol and less from amitriptyline compared with fast metabolizers in the first treatment week (P < 0.01).	Tramadol	70-78	cytochrome P450 2D6	Homo sapiens	0-20
15906019-21	2005	CONCLUSIONS: The EMs and PMs of CYP2D6 treated with tramadol behaved differently in static and dynamic pupillometry.	Tramadol	52-60	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	32-38
16296359-7	2005	Tramadol inhibits the muscarinic receptor, serotonin receptor, and nicotinic acetylcholine receptor ion-channel, suggesting these receptors might be related to the mechanisms of action of tramadol.	Tramadol	0-8	cholinergic receptor nicotinic alpha 2 subunit	Rattus norvegicus	67-99
16296359-7	2005	Tramadol inhibits the muscarinic receptor, serotonin receptor, and nicotinic acetylcholine receptor ion-channel, suggesting these receptors might be related to the mechanisms of action of tramadol.	Tramadol	188-196	cholinergic receptor nicotinic alpha 2 subunit	Rattus norvegicus	67-99
16171665-1	2005	STUDY OBJECTIVE: To investigate the effect of tramadol on the production of serum interleukin (IL) 6, IL-10, and IL-2 and soluble (s) IL-2 receptor (R), thereby evaluating its effects on the proinflammatory and anti-inflammatory responses and immune function in cancer patients undergoing conventional pulmonary lobectomy.	Tramadol	46-54	interleukin 6	Homo sapiens	82-100
16171665-1	2005	STUDY OBJECTIVE: To investigate the effect of tramadol on the production of serum interleukin (IL) 6, IL-10, and IL-2 and soluble (s) IL-2 receptor (R), thereby evaluating its effects on the proinflammatory and anti-inflammatory responses and immune function in cancer patients undergoing conventional pulmonary lobectomy.	Tramadol	46-54	interleukin 2	Homo sapiens	113-117
16171665-1	2005	STUDY OBJECTIVE: To investigate the effect of tramadol on the production of serum interleukin (IL) 6, IL-10, and IL-2 and soluble (s) IL-2 receptor (R), thereby evaluating its effects on the proinflammatory and anti-inflammatory responses and immune function in cancer patients undergoing conventional pulmonary lobectomy.	Tramadol	46-54	interleukin 2	Homo sapiens	134-138
16171665-16	2005	As tramadol was associated with increased IL-2 and delayed enhancement of sIL-2R in our study, it may attenuate to some extent an impaired immune response in pulmonary lobectomy.	Tramadol	3-11	interleukin 2	Homo sapiens	42-46
15951326-0	2005	Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	69-89
15951326-13	2005	CYP2D6 activity was observed as early as 25 weeks PCA, but the impact of CYP2D6 polymorphism on the variability in pharmacokinetics, metabolism and pharmacodynamics of tramadol remains to be established.	Tramadol	168-176	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	73-79
15961977-1	2005	BACKGROUND AND OBJECTIVE: Polymorphic cytochrome P450 (CYP) 2D6 activity has been shown to be a determinant of the pharmacokinetics and pharmacodynamics of tramadol via hepatic phase I O -demethylation of (+)-tramadol to (+)-O-desmethyltramadol.	Tramadol	205-217	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	38-63
15961977-2	2005	Our objective was to investigate whether tramadol can be used as a probe for CYP2D6 phenotyping by determining the concordance between the 8-hour tramadol and 12-hour sparteine metabolic urinary ratios.	Tramadol	41-49	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	77-83
15961977-13	2005	CONCLUSION: Fifty milligrams of tramadol is an alternative CYP2D6 phenotype probe by use of the 8-hour urinary ratio of (-)-M1/(+)-M1.	Tramadol	32-40	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	59-65
15961977-1	2005	BACKGROUND AND OBJECTIVE: Polymorphic cytochrome P450 (CYP) 2D6 activity has been shown to be a determinant of the pharmacokinetics and pharmacodynamics of tramadol via hepatic phase I O -demethylation of (+)-tramadol to (+)-O-desmethyltramadol.	Tramadol	156-164	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	38-63
15903129-0	2005	Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol.	Tramadol	130-138	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-33
15777775-0	2005	Role of 5-HT1A and 5-HT1B receptors in the antinociceptive effect of tramadol.	Tramadol	69-77	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	8-25
15777775-6	2005	These results account for involvement of the somatodendritic 5-HT1A receptors in the analgesic effect of tramadol and support the supraspinal interaction of serotonin and the opioid system in the regulation of pain.	Tramadol	105-113	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	61-67
15509185-12	2004	The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4.	Tramadol	23-31	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	96-121
15742426-0	2005	Trial of tramadol/acetaminophen tablets for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug.	Tramadol	9-17	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	88-93
15482390-6	2004	The interindividual coefficient of variation of ClT (48.56%) was higher than that of Vd (38.09%), indicating the presence of other possible influencing factors on tramadol"s ClT such as CYP2D6 polymorphism, gender and age.	Tramadol	163-171	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	186-192
15197521-0	2004	Increased liability of tramadol-warfarin interaction in individuals with mutations in the cytochrome P450 2D6 gene.	Tramadol	23-31	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	90-109
15197521-1	2004	OBJECTIVE: This study aimed to investigate the importance of cytochrome P(450) enzymes for the reported interaction between tramadol and warfarin.	Tramadol	124-132	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	61-78
15197521-6	2004	CONCLUSION: The liability to an interaction between tramadol and warfarin may be related to the CYP2D6 activity.	Tramadol	52-60	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	96-102
15060515-0	2004	Tramadol pharmacokinetics and its possible interactions with cyclooxygenase 2-selective nonsteroidal anti-inflammatory drugs.	Tramadol	0-8	prostaglandin-endoperoxide synthase 2	Homo sapiens	61-77
15212192-1	2004	The purpose of this clinical trial was to compare the pharmacokinetics of a recently developed fast-release orodispersible tramadol tablet (CAS 27203-92-5, Zamadol Melt) to that of a conventional tramadol capsule.	Tramadol	123-131	BCAR1 scaffold protein, Cas family member	Homo sapiens	140-143
15276689-5	2004	The oral and intrathecally administered tramadol, a mu-opioid and naproxen, a nonselective COX inhibitor produced dose-dependent antinociception, however, rofecoxib, a selective COX-2 inhibitor lacked analgesic efficacy in writhing test.	Tramadol	40-48	cytochrome c oxidase II, mitochondrial	Mus musculus	178-183
15276689-9	2004	The results demonstrated marked synergistic interaction between naproxen and tramadol and such interaction involved opioid as well as non-opioid mechanisms of tramadol and inhibition of COX-1 but not COX-2 by naproxen.	Tramadol	77-85	cytochrome c oxidase I, mitochondrial	Mus musculus	186-191
15509185-12	2004	The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4.	Tramadol	23-31	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	169-175
15509185-12	2004	The O-demethylation of tramadol to M1, the main analgesic effective metabolite, is catalysed by cytochrome P450 (CYP) 2D6, whereas N-demethylation to M2 is catalysed by CYP2B6 and CYP3A4.	Tramadol	23-31	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	180-186
17523716-9	2004	More tramadol BID patients reported dizziness/vertigo (37% vs 26%), vomiting (14% vs 8%) and headache (18% vs 13%) while tramadol OAD patients reported more somnolence (30% vs 21%).	Tramadol	5-13	BH3 interacting domain death agonist	Homo sapiens	14-17
14705234-0	2004	Efficacy and safety of tramadol/acetaminophen tablets (Ultracet) as add-on therapy for osteoarthritis pain in subjects receiving a COX-2 nonsteroidal antiinflammatory drug: a multicenter, randomized, double-blind, placebo-controlled trial.	Tramadol	23-31	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	131-136
14705234-10	2004	CONCLUSION: Tramadol 37.5 mg/APAP 325 mg combination tablets were effective and safe as add-on therapy with COX-2 NSAID for treatment of OA pain.	Tramadol	12-20	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	108-113
14624403-0	2003	A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol.	Tramadol	74-82	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	19-25
14636839-7	2003	The synovial fluid concentrations of SP were significantly reduced only by the treatment with tramadol.	Tramadol	94-102	tachykinin precursor 1	Homo sapiens	37-39
14624403-3	2003	We therefore developed a robust assay that detects common CYP2D6 alleles within 60 minutes of blood withdrawal and links carriers of the variant CYP2D6*3 and *4 alleles to the pharmacokinetics of tramadol.	Tramadol	196-204	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	58-64
14624403-3	2003	We therefore developed a robust assay that detects common CYP2D6 alleles within 60 minutes of blood withdrawal and links carriers of the variant CYP2D6*3 and *4 alleles to the pharmacokinetics of tramadol.	Tramadol	196-204	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	145-151
14624403-5	2003	We determined the genotypes of 100 healthy unrelated individuals and studied the pharmacokinetics of tramadol in 24 CYP2D6 genotyped healthy subjects.	Tramadol	101-109	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	116-122
14624403-8	2003	We observed a statistically significant correlation between plasma tramadol AUC and production of the O-desmethyl metabolite in CYP2D6 genotyped healthy volunteers.	Tramadol	67-75	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	128-134
12893130-3	2003	To aid interpretation of the forensic toxicology results, we studied how the genetic variation of the CYP2D6 gene is reflected in tramadol metabolite ratios found in post-mortem samples.	Tramadol	130-138	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	102-108
14499440-0	2003	Impact of CYP2D6 genotype on postoperative tramadol analgesia.	Tramadol	43-51	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	10-16
14499440-12	2003	PM for CYP2D6 showed a lower response rate to postoperative tramadol analgesia than EM.	Tramadol	60-68	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	7-13
14499440-13	2003	Therefore, CYP2D6 genotype has an impact on analgesia with tramadol.	Tramadol	59-67	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	11-17
12893130-0	2003	Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood.	Tramadol	94-102	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	28-34
12893130-1	2003	Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.	Tramadol	0-8	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	53-68
12893130-1	2003	Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.	Tramadol	0-8	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	70-73
12893130-1	2003	Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	93-99
12893130-1	2003	Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.	Tramadol	149-157	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	53-68
12893130-1	2003	Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.	Tramadol	149-157	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	70-73
12893130-5	2003	As expected, we found a correlation between the number of functional CYP2D6 alleles and the ratio of tramadol to O-demethyltramadol.	Tramadol	101-109	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	69-75
12191703-0	2002	Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects.	Tramadol	15-23	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	45-51
12893130-1	2003	Tramadol is an opioid drug metabolised in phase I by cytochrome P450 (CYP) enzymes, of which CYP2D6 is mainly responsible for the O-demethylation of tramadol, but is not involved in N-demethylation.	Tramadol	149-157	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	93-99
12749738-4	2003	The addition of one or two tramadol/paracetamol 37.5/32 5mg tablets (up to four times daily) for 5 days to existing NSAID or cyclo-oxygenase-2 inhibitor analgesic therapy provided effective pain relief in patients with osteoarthritis flare pain.	Tramadol	27-35	prostaglandin-endoperoxide synthase 2	Homo sapiens	125-142
12191703-1	2002	The aim of the present study is to investigate the influence of the CYP2D6*10 allele on the disposition of tramadol hydrochloride in Malaysian subjects.	Tramadol	107-129	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	68-74
12191703-9	2002	Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test).	Tramadol	102-110	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	33-39
12191703-11	2002	CYP2D6 activity may play a main role in determining tramadol pharmacokinetics.	Tramadol	52-60	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
12191703-12	2002	The CYP2D6*10 allele particularly was associated with higher serum levels of tramadol compared with the CYP2D6*1 allele.	Tramadol	77-85	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	4-10
11911558-13	2002	CONCLUSION: In this study, addition of tramadol/acetaminophen to NSAID or COX-2-selective inhibitor therapy was well tolerated and effective in the treatment of OA flare pain.	Tramadol	39-47	mitochondrially encoded cytochrome c oxidase II	Homo sapiens	74-79
11916794-0	2002	Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells.	Tramadol	0-8	solute carrier family 6 member 2	Bos taurus	18-44
11916794-5	2002	Saturation analysis revealed that tramadol increased the apparent Michaelis constant of [3H]-NE uptake without changing the maximal velocity, indicating that inhibition occurred via competition for the NET (inhibition constant, K(i) = 13.7 microM).	Tramadol	34-42	solute carrier family 6 member 2	Bos taurus	202-205
11916794-9	2002	These findings indicate that tramadol competitively inhibits NET function at desipramine-binding sites.	Tramadol	29-37	solute carrier family 6 member 2	Bos taurus	61-64
11916794-10	2002	IMPLICATIONS: Tramadol competitively inhibits norepinephrine transporter function at desipramine-binding sites in the adrenal medullary cells and probably the noradrenergic neurons of the descending inhibitory system.	Tramadol	14-22	solute carrier family 6 member 2	Bos taurus	46-72
11808821-1	2002	Cytochrome P4502D6 (CYP2D6) activity has been shown to be a determinant of both the pharmacokinetics and pharmacodynamics of tramadol in adults.	Tramadol	125-133	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-18
11808821-1	2002	Cytochrome P4502D6 (CYP2D6) activity has been shown to be a determinant of both the pharmacokinetics and pharmacodynamics of tramadol in adults.	Tramadol	125-133	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	20-26
11808821-7	2002	Thus, the number of functional CYP2D6 alleles and the availability of alternative cytochromes P450 capable of metabolizing tramadol may explain the poor association between DM, a well-characterized CYP2D6 probe, and tramadol in a population of CYP2D6 extensive metabolizers.	Tramadol	123-131	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	198-204
11808821-2	2002	This study evaluated the association between CYP2D6 activity, as determined by dextromethorphan (DM) urinary metabolite ratio, and tramadol biotransformation in 13 children (7-16 years).	Tramadol	131-139	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	45-51
11808821-7	2002	Thus, the number of functional CYP2D6 alleles and the availability of alternative cytochromes P450 capable of metabolizing tramadol may explain the poor association between DM, a well-characterized CYP2D6 probe, and tramadol in a population of CYP2D6 extensive metabolizers.	Tramadol	123-131	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	198-204
11050366-5	2000	Moreover, (+/-)8-OH-DPAT (0.125-1 mg/kg, s.c.), a selective 5-HT(1A) agonist, reduces the analgesic effect of tramadol in the same tests.	Tramadol	110-118	5-hydroxytryptamine receptor 1A	Rattus norvegicus	60-67
11454734-0	2001	Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes.	Tramadol	60-72	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	18-34
11454734-1	2001	The metabolism of cis-tramadol has been studied in human liver microsomes and in cDNA-expressed human cytochrome P-450 (CYP) isoforms.	Tramadol	18-30	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	102-118
11454734-1	2001	The metabolism of cis-tramadol has been studied in human liver microsomes and in cDNA-expressed human cytochrome P-450 (CYP) isoforms.	Tramadol	18-30	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	120-123
11454734-4	2001	Kinetic analysis revealed that multiple CYP enzymes were involved in the metabolism of tramadol to both M1 and M2.	Tramadol	87-95	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	40-43
11454734-7	2001	In studies with characterized human liver microsomal preparations, good correlations were observed between tramadol metabolism to M1 and M2 and enzymatic markers of CYP2D6 and CYP2B6, respectively.	Tramadol	107-115	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	176-182
11454734-8	2001	Tramadol was metabolized to M1 by cDNA-expressed CYP2D6 and to M2 by CYP2B6 and CYP3A4.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	49-55
11454734-8	2001	Tramadol was metabolized to M1 by cDNA-expressed CYP2D6 and to M2 by CYP2B6 and CYP3A4.	Tramadol	0-8	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	69-75
11454734-8	2001	Tramadol was metabolized to M1 by cDNA-expressed CYP2D6 and to M2 by CYP2B6 and CYP3A4.	Tramadol	0-8	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	80-86
11454734-9	2001	Tramadol metabolism in human liver microsomes to M1 and M2 was markedly inhibited by the CYP2D6 inhibitor quinidine and the CYP3A4 inhibitor troleandomycin, respectively.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	89-95
11454734-9	2001	Tramadol metabolism in human liver microsomes to M1 and M2 was markedly inhibited by the CYP2D6 inhibitor quinidine and the CYP3A4 inhibitor troleandomycin, respectively.	Tramadol	0-8	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	124-130
11454734-11	2001	By kinetic analysis and the results of the reaction phenotyping studies, tramadol metabolism in human liver is catalyzed by multiple CYP isoforms.	Tramadol	73-81	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	133-136
11050366-6	2000	These results suggest an implication of the somatodendritic 5-HT(1A) receptors in the analgesic effect of tramadol and open a new adjuvant analgesic strategy for the use of this compound.	Tramadol	106-114	5-hydroxytryptamine receptor 1A	Rattus norvegicus	60-67
8982709-0	1996	Tramadol, M1 metabolite and enantiomer affinities for cloned human opioid receptors expressed in transfected HN9.10 neuroblastoma cells.	Tramadol	0-8	MT-RNR2 like 9 (pseudogene)	Homo sapiens	109-112
11124014-2	2000	In this study, we evaluated the putative activity of tramadol to suppress prostaglandin endoperoxide synthase-1 (PGHS-1), and prostaglandin endoperoxide synthase-2 (PGHS-2) activities in human whole blood in vitro.	Tramadol	53-61	prostaglandin-endoperoxide synthase 1	Homo sapiens	74-111
11124014-2	2000	In this study, we evaluated the putative activity of tramadol to suppress prostaglandin endoperoxide synthase-1 (PGHS-1), and prostaglandin endoperoxide synthase-2 (PGHS-2) activities in human whole blood in vitro.	Tramadol	53-61	prostaglandin-endoperoxide synthase 1	Homo sapiens	113-119
11124014-2	2000	In this study, we evaluated the putative activity of tramadol to suppress prostaglandin endoperoxide synthase-1 (PGHS-1), and prostaglandin endoperoxide synthase-2 (PGHS-2) activities in human whole blood in vitro.	Tramadol	53-61	prostaglandin-endoperoxide synthase 2	Homo sapiens	126-163
10778358-2	1999	Tramadol is metabolized by cytochromoxidase CYP2D6 to O-desmethyl-tramadol with opioid agonist activity.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	44-50
9337439-7	1997	The patient was phenotyped for CYP2D6 activity, the major metabolic pathway for tramadol elimination, and was determined to be an extensive metabolizer with very high CYP2D6 activity.	Tramadol	80-88	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	31-37
9337439-7	1997	The patient was phenotyped for CYP2D6 activity, the major metabolic pathway for tramadol elimination, and was determined to be an extensive metabolizer with very high CYP2D6 activity.	Tramadol	80-88	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	167-173
9313273-3	1997	After acute subcutaneous administration, tramadol induced antinociception starting from a dose of 20 mg/kg, whereas it significantly enhanced natural killer activity and IL-2 production at doses as low as 1 mg/kg and splenocyte proliferation starting from a dose of 10 mg/kg.	Tramadol	41-49	interleukin 2	Mus musculus	170-174
10793594-7	2000	injection (n = 9), the mean elimination half-life of tramadol was 6.4 (SD 2.7) h, with a volume of distribution of 3.1 (1.1) litre kg-1 and total plasma clearance of 6.1 (2.5) ml kg-1 min-1.	Tramadol	53-61	CD59 molecule (CD59 blood group)	Homo sapiens	184-189
10670117-16	1999	At 6 and 9 min, the MAP and DAP were significantly higher in tramadol than in fentanyl group (P < 0.05).	Tramadol	61-69	death associated protein	Homo sapiens	28-31
9034418-8	1997	Tramadol is metabolized to an active metabolite, M1, by the CYP2D6 enzyme.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
9034418-9	1997	If this metabolite has less serotonergic activity than tramadol, inhibition of CYP2D6 by sertraline could have been a factor in the interaction.	Tramadol	55-63	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	79-85
9476037-0	1997	Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol.	Tramadol	68-76	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	12-18
9476037-1	1997	OBJECTIVE: This study was designed to investigate whether the in vivo metabolism of tramadol was influenced by CYP2D6 polymorphism.	Tramadol	84-92	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	111-117
9476037-7	1997	These in vivo results confirm that tramadol O-demethylation is carried out to a large extent by the polymorphic CYP2D6.	Tramadol	35-43	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	112-118
8925281-0	1995	Attenuation of c-Fos expression in the rat lumbosacral spinal cord by morphine or tramadol following noxious colorectal distention.	Tramadol	82-90	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	15-20
8988065-0	1996	The hypoalgesic effect of tramadol in relation to CYP2D6.	Tramadol	26-34	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	50-56
8988065-8	1996	It is concluded that formation of (+)-M1 by way of CYP2D6 is important for the effect of tramadol on experimental pain.	Tramadol	89-97	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	51-57
8925281-2	1995	This study examined the effects of the analgesics morphine and tramadol on c-Fos expression resulting from noxious CRD in the rat.	Tramadol	63-71	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	75-80
8925281-4	1995	with morphine (1.25 mg/kg-5.0 mg/kg) or tramadol (1 mg/kg-20 mg/kg) dose-dependently attenuated c-Fos expression to CRD in all areas of the L6-S1 spinal gray matter.	Tramadol	40-48	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	96-101
8925281-8	1995	However, the dose of tramadol that eliminated the visceromotor response (7% of control) reduced the c-Fos expression to 47% of control.	Tramadol	21-29	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	100-105
33812699-7	2021	Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels.	Tramadol	147-155	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	28-34
8272795-3	1993	The influence of naloxone and quinidine (a selective P450DB1 or CAP2D6 inhibitor) on tramadol effect was investigated crossover and double-blind vs placebo in healthy subjects.	Tramadol	85-93	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	53-60
8272795-13	1993	Quinidine blockade of tramadol myosis suggests that the mu agonist component of tramadol effect results from its O-demethylation by the polymorphic P450DB1 enzyme.	Tramadol	22-30	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	148-155
8272795-13	1993	Quinidine blockade of tramadol myosis suggests that the mu agonist component of tramadol effect results from its O-demethylation by the polymorphic P450DB1 enzyme.	Tramadol	80-88	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	148-155
2135015-8	1990	Minimum effective tramadol serum concentration (MEC) varied greatly and could be best described by a log-normal distribution (range 20.2-986.3 ng/ml, median 287.7 ng/ml).	Tramadol	18-26	C-C motif chemokine ligand 28	Homo sapiens	48-51
33818692-7	2021	Our results illustrated a significant drop in VEGF (vascular endothelial growth factor) level in the tramadol group.	Tramadol	101-109	vascular endothelial growth factor A	Rattus norvegicus	46-50
33818692-7	2021	Our results illustrated a significant drop in VEGF (vascular endothelial growth factor) level in the tramadol group.	Tramadol	101-109	vascular endothelial growth factor A	Rattus norvegicus	52-86
33812699-7	2021	Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels.	Tramadol	147-155	ATP binding cassette subfamily B member 1	Homo sapiens	90-95
33385878-6	2021	The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP).	Tramadol	32-40	interleukin 6	Homo sapiens	117-135
33385878-6	2021	The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP).	Tramadol	32-40	tumor necrosis factor	Homo sapiens	137-164
33385878-6	2021	The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP).	Tramadol	32-40	tumor necrosis factor	Homo sapiens	166-175
33385878-6	2021	The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP).	Tramadol	32-40	C-reactive protein	Homo sapiens	182-200
33385878-6	2021	The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP).	Tramadol	32-40	C-reactive protein	Homo sapiens	202-205
33385878-7	2021	Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2.	Tramadol	9-17	interleukin 2	Homo sapiens	73-77
34923198-0	2022	Vitamin B12 ameliorate Tramadol-induced oxidative stress, endocrine imbalance, apoptosis and NO/iNOS/NF-kappaB expression in Sprague Dawley rats through regulatory mechanism in the pituitary-gonadal axis.	Tramadol	23-31	nitric oxide synthase 2	Rattus norvegicus	96-100
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	interleukin 1 alpha	Rattus norvegicus	210-218
32797786-0	2020	Tramadol Effects on Lameness Score After Inhibition of P-GP by Ivermectin Administration in Horses: Preliminary Results.	Tramadol	0-8	ATP binding cassette subfamily B member 1	Equus caballus	55-59
32797786-1	2020	This study aimed to evaluate the effects and lameness degree in horses administered tramadol after the P-glycoprotein (P-gp) enteric inhibitor ivermectin.	Tramadol	84-92	ATP binding cassette subfamily B member 1	Equus caballus	103-117
32797786-1	2020	This study aimed to evaluate the effects and lameness degree in horses administered tramadol after the P-glycoprotein (P-gp) enteric inhibitor ivermectin.	Tramadol	84-92	ATP binding cassette subfamily B member 1	Equus caballus	119-123
32797786-8	2020	However, future studies should be conducted to assess the interaction between P-gp inhibitors on the pharmacokinetics of tramadol.	Tramadol	121-129	ATP binding cassette subfamily B member 1	Equus caballus	78-82
1596676-14	1992	The results provide evidence for an interaction of tramadol with the neuronal 5-HT transporter.	Tramadol	51-59	solute carrier family 6 member 4	Rattus norvegicus	78-94
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	interleukin 6	Rattus norvegicus	220-224
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	transcription factor A, mitochondrial	Rattus norvegicus	156-161
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	tumor necrosis factor	Rattus norvegicus	226-235
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	caspase 3	Rattus norvegicus	241-250
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	uncoupling protein 2	Rattus norvegicus	167-171
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	173-176
34923198-5	2022	Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-kappaB, IL-1beta, IL-6, TNF-alpha, and caspase-3 activity.	Tramadol	0-8	nitric oxide synthase 2	Rattus norvegicus	193-197
34383318-0	2022	Physiologically-based Pharmacokinetic Modeling to Assess the Impact of CYP2D6-Mediated Drug-Drug Interactions on Tramadol and O-Desmethyltramadol Exposures via Allosteric and Competitive Inhibition.	Tramadol	113-121	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	71-77
34383318-9	2022	In fact, tramadol is predicted to act as a CYP2D6 perpetrator and increase metoprolol exposure, which may necessitate the need for dose separation.	Tramadol	9-17	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	43-49
34383318-2	2022	CYP2D6 inhibition could be important for tramadol as it decreases the formation of its pharmacologically active metabolite, O-desmethyltramadol, potentially resulting in increased opioid use and misuse.	Tramadol	41-49	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
34383318-3	2022	The objective of this study was to evaluate the impact of allosteric and competitive CYP2D6 inhibition on tramadol and O-desmethyltramadol pharmacokinetics using quinidine and metoprolol as prototypical perpetrator drugs.	Tramadol	106-114	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	85-91
34383318-5	2022	Our results show that there is a differentiated impact of CYP2D6 inhibitors on tramadol and O-desmethyltramadol based on their mechanisms of inhibition.	Tramadol	79-87	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	58-64
34783063-9	2021	Furthermore, daily i.p injection of tramadol significantly suppressed CGRP expression in DRG (p < 0.0001).	Tramadol	36-44	calcitonin-related polypeptide alpha	Rattus norvegicus	70-74
34744722-1	2021	Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH).	Tramadol	99-107	pregnancy-induced hypertension (pre-eclampsia, eclampsia, toxemia of pregnancy included)	Homo sapiens	182-185
34764420-9	2021	Serum levels of IL-6 and TNFalpha were reduced in both tramadol-treated group 1 and 2 compared to the control group.	Tramadol	55-63	interleukin 6	Homo sapiens	16-20
34764420-9	2021	Serum levels of IL-6 and TNFalpha were reduced in both tramadol-treated group 1 and 2 compared to the control group.	Tramadol	55-63	tumor necrosis factor	Homo sapiens	25-33
34764420-8	2021	The expression levels of ERalpha, PRalpha and beta, and TRPV1 were decreased in tramadol group 2 compared with those in the morphine group, but not compared to the control group.	Tramadol	80-88	estrogen receptor 1	Homo sapiens	25-32
34764420-8	2021	The expression levels of ERalpha, PRalpha and beta, and TRPV1 were decreased in tramadol group 2 compared with those in the morphine group, but not compared to the control group.	Tramadol	80-88	S100 calcium binding protein A6	Homo sapiens	34-50
34764420-8	2021	The expression levels of ERalpha, PRalpha and beta, and TRPV1 were decreased in tramadol group 2 compared with those in the morphine group, but not compared to the control group.	Tramadol	80-88	transient receptor potential cation channel subfamily V member 1	Homo sapiens	56-61
34423496-13	2021	CONCLUSION: CYP2D6 genotype may identify cancer patients at increased risk for inadequate analgesia when treated with typical first-line opioids like codeine, tramadol, or standard-dose hydrocodone.	Tramadol	159-167	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	12-18
34565798-0	2021	Correction: Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone).	Tramadol	133-141	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	104-110
34607473-6	2021	Multivariable analyses showed that among prescription opioids, acetaminophen with opioid (IRR = 1.17, 95% CI = 1.11-1.24) and tramadol (IRR = 1.12, 95% CI = 1.06-1.47) were associated with higher risk of suspected suicides than intentional misuse/abuse without suicidal intent.	Tramadol	126-134	insulin receptor related receptor	Homo sapiens	136-139
34480795-1	2021	Tramadol (TR) metabolism is mainly dependent on the enzymatic activity of CYP2D6, which is controlled by genetic polymorphisms.	Tramadol	0-8	coagulation factor II thrombin receptor	Homo sapiens	10-12
34548593-8	2021	Tramadol upregulated the expression of oxidative stress and inflammatory markers in mice heart and aorta, whereas downregulated eNOS expression.	Tramadol	0-8	nitric oxide synthase 3, endothelial cell	Mus musculus	128-132
34480795-1	2021	Tramadol (TR) metabolism is mainly dependent on the enzymatic activity of CYP2D6, which is controlled by genetic polymorphisms.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	74-80
34468866-3	2021	Here, we have studied the interaction between 2-hydroxypropyl beta-CD (HPbetaCD) and three water-soluble drugs, namely naloxone (NX), oxycodone (OC), and tramadol (TR), by isothermal titration calorimetry (ITC) combined with molecular modeling in view of the potential impact on drug release.	Tramadol	154-162	ACD shelterin complex subunit and telomerase recruitment factor	Homo sapiens	62-69
34392133-0	2021	Amplification by tramadol of PGD2-induced osteoprotegerin synthesis in osteoblasts: Involvement of mu-opioid receptor and 5-HT transporter.	Tramadol	17-25	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	42-57
34392133-1	2021	Tramadol, a weak mu-opioid receptor (MOR) agonist with inhibitory effects on the reuptake of serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine, is an effective analgesic to chronic pains.	Tramadol	0-8	opioid receptor, mu 1	Mus musculus	17-35
34392133-1	2021	Tramadol, a weak mu-opioid receptor (MOR) agonist with inhibitory effects on the reuptake of serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine, is an effective analgesic to chronic pains.	Tramadol	0-8	opioid receptor, mu 1	Mus musculus	37-40
34319855-1	2021	The aim of this study was to compare the in vitro cytotoxic effect of tramadol and M1 metabolite in HepG2 cell line, the underlying mechanism, and PI3K/AKT/mTOR as potential target.	Tramadol	70-78	AKT serine/threonine kinase 1	Homo sapiens	152-155
34319855-1	2021	The aim of this study was to compare the in vitro cytotoxic effect of tramadol and M1 metabolite in HepG2 cell line, the underlying mechanism, and PI3K/AKT/mTOR as potential target.	Tramadol	70-78	mechanistic target of rapamycin kinase	Homo sapiens	156-160
34319855-8	2021	For PI3K/AKT/mTOR pathway, therapeutic concentration of tramadol was only able to increase phosphorylation of AKT while higher toxic concentrations were able to increase phosphorylation of whole pathway; Meanwhile, M1 metabolite was able to increase the phosphorylation of the whole pathway significantly in therapeutic and toxic concentrations.	Tramadol	56-64	AKT serine/threonine kinase 1	Homo sapiens	9-12
34392133-4	2021	Herein, we investigated the mechanism underlying the effect of tramadol on the PGD2-induced osteoprotegerin synthesis in these cells.	Tramadol	63-71	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	92-107
34392133-5	2021	Tramadol enhanced the PGD2-induced release and mRNA expression of osteoprotegerin.	Tramadol	0-8	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	66-81
34392133-6	2021	Naloxone, a MOR antagonist, reduced the amplification by tramadol of the PGD2-stimulated osteoprotegerin release.	Tramadol	57-65	opioid receptor, mu 1	Mus musculus	12-15
34392133-6	2021	Naloxone, a MOR antagonist, reduced the amplification by tramadol of the PGD2-stimulated osteoprotegerin release.	Tramadol	57-65	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	89-104
34392133-8	2021	Tramadol enhanced PGD2-stimulated phosphorylation of p38 MAP kinase and SAPK/JNK, but not p44/p42 MAP kinase.	Tramadol	0-8	mitogen-activated protein kinase 8	Mus musculus	77-80
34392133-9	2021	Both SB203580 and SP600125 suppressed the tramadol effect to enhance the PGD2-stimulated osteoprotegerin release.	Tramadol	42-50	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	89-104
34392133-10	2021	Tramadol enhanced the PGE2-induced osteoprotegerin release as well as PGD2.	Tramadol	0-8	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	35-50
34392133-11	2021	These results suggest that tramadol amplifies the PGD2-induced osteoprotegerin synthesis at the upstream of p38 MAP kinase and SAPK/JNK in the involvement of both MOR and 5-HT transporter in osteoblasts.	Tramadol	27-35	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	63-78
34392133-11	2021	These results suggest that tramadol amplifies the PGD2-induced osteoprotegerin synthesis at the upstream of p38 MAP kinase and SAPK/JNK in the involvement of both MOR and 5-HT transporter in osteoblasts.	Tramadol	27-35	mitogen-activated protein kinase 8	Mus musculus	132-135
34392133-11	2021	These results suggest that tramadol amplifies the PGD2-induced osteoprotegerin synthesis at the upstream of p38 MAP kinase and SAPK/JNK in the involvement of both MOR and 5-HT transporter in osteoblasts.	Tramadol	27-35	opioid receptor, mu 1	Mus musculus	163-166
34468866-3	2021	Here, we have studied the interaction between 2-hydroxypropyl beta-CD (HPbetaCD) and three water-soluble drugs, namely naloxone (NX), oxycodone (OC), and tramadol (TR), by isothermal titration calorimetry (ITC) combined with molecular modeling in view of the potential impact on drug release.	Tramadol	154-162	coagulation factor II thrombin receptor	Homo sapiens	164-166
34319855-8	2021	For PI3K/AKT/mTOR pathway, therapeutic concentration of tramadol was only able to increase phosphorylation of AKT while higher toxic concentrations were able to increase phosphorylation of whole pathway; Meanwhile, M1 metabolite was able to increase the phosphorylation of the whole pathway significantly in therapeutic and toxic concentrations.	Tramadol	56-64	mechanistic target of rapamycin kinase	Homo sapiens	13-17
34319855-8	2021	For PI3K/AKT/mTOR pathway, therapeutic concentration of tramadol was only able to increase phosphorylation of AKT while higher toxic concentrations were able to increase phosphorylation of whole pathway; Meanwhile, M1 metabolite was able to increase the phosphorylation of the whole pathway significantly in therapeutic and toxic concentrations.	Tramadol	56-64	AKT serine/threonine kinase 1	Homo sapiens	110-113
34211690-10	2021	To reduce the risk of confounding by indication, the RORs for tramadol compared with other opioids were obtained.	Tramadol	62-70	receptor tyrosine kinase like orphan receptor 1	Homo sapiens	53-57
34246203-4	2021	The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain.	Tramadol	136-144	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	72-78
34246203-4	2021	The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain.	Tramadol	136-144	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	83-89
34246203-15	2021	CONCLUSIONS: CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac.	Tramadol	70-78	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	13-19
34246203-15	2021	CONCLUSIONS: CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac.	Tramadol	70-78	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	24-30
34318377-4	2021	Under the optimum conditions, the linearity was obtained in the range 1.5 to 700.0 ng mL-1 for morphine, codeine, oxycodone, and tramadol, and 0.5 to 1000.0 ng mL-1 for nalbuphine, thebaine, and noscapine with coefficient of determination (r2) >= 0.9990.	Tramadol	129-137	L1 cell adhesion molecule	Mus musculus	86-90
34287102-11	2022	CONCLUSION: Marked and prolonged serotonin toxicity was attributed to increased M2 production due to paroxetine- and propranolol-related CYP2D6 inhibition of tramadol metabolism.	Tramadol	158-166	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	137-143
34267337-0	2021	Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone).	Tramadol	121-129	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	92-98
34267337-1	2021	The current Dutch Pharmacogenetics Working Group (DPWG) guideline, describes the gene-drug interaction between CYP2D6 and the opioids codeine, tramadol and oxycodone.	Tramadol	143-151	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	111-117
34267337-10	2021	CYP2D6 genotyping is classified as "potentially beneficial" for tramadol and can be considered on an individual patient basis.	Tramadol	64-72	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
34206920-1	2021	In this work, an electrochemically activated screen-printed carbon electrode modified with sodium dodecyl sulfate (aSPCE/SDS) was proposed for the simultaneous determination of paracetamol (PA), diclofenac (DF), and tramadol (TR).	Tramadol	216-224	coagulation factor II thrombin receptor	Homo sapiens	226-228
34211690-14	2021	The ROR for tramadol exposure was 3.35 (95% confidence interval (CI) 2.53-4.43).	Tramadol	12-20	long intergenic non-protein coding RNA, regulator of reprogramming	Homo sapiens	4-7
34211690-15	2021	This association persisted when comparing tramadol with other opioids; ROR: 2.13 (95% CI 1.52-2.99).	Tramadol	42-50	long intergenic non-protein coding RNA, regulator of reprogramming	Homo sapiens	71-74
34520032-5	2021	Among the atypical opioids, tramadol has an advantage of being a Schedule IV drug, and thus having a relatively low abuse potential-but its effects, including its effect on respiratory drive, are dependent on cytochrome P450 2D6 metabolizer status.	Tramadol	28-36	cytochrome P450 2D6	Homo sapiens	209-228
34744277-13	2021	A negative correlation was observed between the preoperative values of CRP and PCT and the analgesic effect of tramadol assessed at the second measurement point (r=-0.358, p=0.03, and r=-0.364, p=0.02, respectively).	Tramadol	111-119	C-reactive protein	Homo sapiens	71-74
34124111-14	2021	Conclusions: Tramadol PCIA after CS in high-risk women can help to reduce the risk of PPD at 4 weeks after elective CS.	Tramadol	13-21	citrate synthase	Homo sapiens	116-118
34513628-6	2021	Tramadol, as an opioid-like analgesic, is mainly metabolized into O-desmethyl tramadol (M1), by CYP2D6 and undergoes N-demethylation to M2, by CYP2B6 and CYP3A4.	Tramadol	0-8	cytochrome P450, family 2, subfamily d, polypeptide 4	Rattus norvegicus	96-102
34513628-6	2021	Tramadol, as an opioid-like analgesic, is mainly metabolized into O-desmethyl tramadol (M1), by CYP2D6 and undergoes N-demethylation to M2, by CYP2B6 and CYP3A4.	Tramadol	0-8	cytochrome P450, family 2, subfamily b, polypeptide 3	Rattus norvegicus	143-149
3778568-2	1986	The absolute bioavailability of tramadol hydrochloride (rac-1(e)-(m-methoxyphenyl)-2-(e)-(dimethylaminomethyl)cyclohexan- 1(a)-ol hydrochloride, CG 315) after the oral administration of Tramal capsules was determined in a balanced cross-over study in 10 male volunteers.	Tramadol	32-54	Rac family small GTPase 1	Homo sapiens	56-61
34719650-0	2021	Involvement of the Peripheral mu-Opioid Receptor in Tramadol-Induced Constipation in Rodents.	Tramadol	52-60	opioid receptor, mu 1	Mus musculus	30-48
34719650-1	2021	Tramadol is a weak opioid that produces analgesic effect via both the mu-opioid receptor (MOR) and non-opioid targets.	Tramadol	0-8	opioid receptor, mu 1	Mus musculus	70-88
34719650-1	2021	Tramadol is a weak opioid that produces analgesic effect via both the mu-opioid receptor (MOR) and non-opioid targets.	Tramadol	0-8	opioid receptor, mu 1	Mus musculus	90-93
34719650-12	2021	These results suggest that peripheral MOR participates in tramadol-induced constipation.	Tramadol	58-66	opioid receptor, mu 1	Mus musculus	38-41
35155248-4	2022	Methods: The effects of tramadol on two different subtypes of human breast adenocarcinoma cell lines, MDA-MB-231 and MCF-7, were studied with regard to cell growth, migration, colony formation and invasion and normoxic or hypoxic microenvironment for the expression of hypoxia-inducible factor-1alpha, reactive oxygen species, epithelial-mesenchymal transition related and cyclin-related proteins.	Tramadol	24-32	hypoxia inducible factor 1 subunit alpha	Homo sapiens	269-300
35155248-6	2022	Results: The results showed that tramadol inhibited cell growth at concentrations more than 0.5 and more than 1.0 mg/mL in MDA-MB-231 and MCF-7 cells, respectively.	Tramadol	33-41	thrombopoietin	Mus musculus	117-119
34982723-8	2022	RESULTS: From the 869 AEs reported, we identified 125 new signals related to tramadol use not listed on the drug label that satisfied all 3 signal detection criteria.	Tramadol	77-85	paired box 5	Homo sapiens	134-139
35349917-6	2022	Under the optimized conditions, linear ranges of 0.1-30 ng mL-1 and 0.1-35 ng mL-1, and detection limits of 73 and 32 pg mL-1, were obtained for tramadol and methadone, respectively.	Tramadol	145-153	L1 cell adhesion molecule	Mus musculus	59-63
35349917-6	2022	Under the optimized conditions, linear ranges of 0.1-30 ng mL-1 and 0.1-35 ng mL-1, and detection limits of 73 and 32 pg mL-1, were obtained for tramadol and methadone, respectively.	Tramadol	145-153	L1 cell adhesion molecule	Mus musculus	78-82
35349917-6	2022	Under the optimized conditions, linear ranges of 0.1-30 ng mL-1 and 0.1-35 ng mL-1, and detection limits of 73 and 32 pg mL-1, were obtained for tramadol and methadone, respectively.	Tramadol	145-153	L1 cell adhesion molecule	Mus musculus	121-125
35313383-11	2022	The findings of this study indicate the potential role of orexin and endocannabinoid systems in mediating the effects of tramadol in mPFC and the possible interaction between the two systems via OX2 and CB1 receptors.	Tramadol	121-129	hypocretin neuropeptide precursor	Rattus norvegicus	58-64
35163308-4	2022	Tramadol administration induced an increase in serum levels of urea, creatinine, uric acid, the renal immune expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and caspase-3 which turned out to be decreased by 10-DHGD intake.	Tramadol	0-8	caspase 3	Rattus norvegicus	203-212
35163308-5	2022	Our results also recorded a significant increase in renal malondialdehyde (MDA), toll-like receptor 4 (TLR4), and extracellular signal-regulated protein kinase-1 (ERK1) along with glutathione (GSH), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) decrease due to tramadol intake, which were counteracted by 10-DHGD administration as illustrated and supported by the histopathological findings.	Tramadol	271-279	mitogen activated protein kinase 3	Rattus norvegicus	163-167
35418262-9	2022	Both early PRF therapy and late PRF therapy combined with early tramadol treatment suppressed NaV1.7 upregulation in the DRG of rats with RTX-induced mechanical allodynia.	Tramadol	64-72	sodium voltage-gated channel alpha subunit 9	Rattus norvegicus	94-100
33575951-1	2021	INTRODUCTION: Recently the DAVID study demonstrated the better analgesic efficacy of tramadol hydrochloride/dexketoprofen 75/25 mg (TRAM/DKP) over tramadol hydrochloride/paracetamol 75/650 mg (TRAM/paracetamol) in a model of moderate to severe acute pain following surgical removal of an impacted third molar.	Tramadol	85-107	translocation associated membrane protein 1	Homo sapiens	132-136
7198474-2	1981	administration of 14C-labelled rac.-1-(e)-(m-methoxyphenyl)-2-(e)-dimethylaminomethyl-cyclohexan-1-(a)-ol hydrochloride (tramadol hydrochloride, CG 315, Tramal) to mice, hamsters, rats, guinea pigs, rabbits, dogs and man the metabolic pathways were investigated and the results compared.	Tramadol	121-143	Rac family small GTPase 1	Mus musculus	31-37
33575951-1	2021	INTRODUCTION: Recently the DAVID study demonstrated the better analgesic efficacy of tramadol hydrochloride/dexketoprofen 75/25 mg (TRAM/DKP) over tramadol hydrochloride/paracetamol 75/650 mg (TRAM/paracetamol) in a model of moderate to severe acute pain following surgical removal of an impacted third molar.	Tramadol	85-107	translocation associated membrane protein 1	Homo sapiens	193-197
33131142-0	2021	Impact of CYP2D6 Activity and Cachexia Progression on Enantiomeric Alteration of Plasma Tramadol and Its Demethylated Metabolites and Their Relationships with Central Nervous System Symptoms in Head and Neck Cancer Patients.	Tramadol	88-96	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	10-16
33932698-0	2021	The role of adenosine A1 receptor in the peripheral tramadol"s effect in the temporomandibular joint of rats.	Tramadol	52-60	adenosine A1 receptor	Rattus norvegicus	12-33
33932698-9	2021	The tramadol"s peripheral anti-inflammatory effect was mediated by the adenosine A1 receptor and was associated with increased protein expression of alpha2a-adrenoceptor in the periarticular tissues (p < 0.05: ANOVA, Tukey"s test).	Tramadol	4-12	adenosine A1 receptor	Rattus norvegicus	71-92
33932698-9	2021	The tramadol"s peripheral anti-inflammatory effect was mediated by the adenosine A1 receptor and was associated with increased protein expression of alpha2a-adrenoceptor in the periarticular tissues (p < 0.05: ANOVA, Tukey"s test).	Tramadol	4-12	adrenoceptor alpha 2A	Rattus norvegicus	149-169
33932698-13	2021	We identify tramadol"s peripheral effect is mediated by adenosine A1 receptor, possibly expressed in macrophages in the TMJ tissue.	Tramadol	12-20	adenosine A1 receptor	Rattus norvegicus	56-77
33932698-14	2021	We also determined an important discovery related to the activation of A1R/alpha2a receptors in the tramadol action.	Tramadol	100-108	spectrin, alpha, non-erythrocytic 1	Rattus norvegicus	75-82
32734768-1	2021	OBJECTIVE: It was reported that the administration of tramadol in patients with cancer pain who have a higher interleukin 6 (IL-6) serum level led to insufficient pain relief.	Tramadol	54-62	interleukin 6	Homo sapiens	110-123
32734768-1	2021	OBJECTIVE: It was reported that the administration of tramadol in patients with cancer pain who have a higher interleukin 6 (IL-6) serum level led to insufficient pain relief.	Tramadol	54-62	interleukin 6	Homo sapiens	125-129
33686610-12	2021	The 90% confidence intervals for Cmax,ss and AUC0-tau geometric mean ratios for tramadol were 93.85-103.31% and 99.04-105.27%.	Tramadol	80-88	microtubule associated protein tau	Homo sapiens	50-53
33131142-1	2021	This study aimed to evaluate the influence of CYP2D6 activity and cachexia progression on the enantiomeric alteration of plasma tramadol and its demethylated metabolites in head and neck cancer patients.	Tramadol	128-136	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	46-52
33131142-7	2021	The plasma concentrations of (+)-tramadol and (+)-ODT were higher in patients with GPS 1 or 2 than in those with GPS 0.	Tramadol	33-41	G protein pathway suppressor 1	Homo sapiens	83-88
33131142-9	2021	In patients with GPS 1 or 2, the plasma (-)-tramadol was associated with the incidence of central nervous system symptoms.	Tramadol	44-52	G protein pathway suppressor 1	Homo sapiens	17-22
33131142-10	2021	In conclusion, CYP2D6 AS partially explained the contribution of CYP2D6 activity to plasma tramadol and its demethylated metabolite enantiomers.	Tramadol	91-99	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	15-21
33131142-10	2021	In conclusion, CYP2D6 AS partially explained the contribution of CYP2D6 activity to plasma tramadol and its demethylated metabolite enantiomers.	Tramadol	91-99	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	65-71
33645892-0	2021	Tramadol aggravates cardiovascular toxicity in a rat model of alcoholism: Involvement of intermediate microfilament proteins and immune-expressed osteopontin.	Tramadol	0-8	secreted phosphoprotein 1	Rattus norvegicus	146-157
32440822-5	2020	Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2"-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities.	Tramadol	0-12	catalase	Rattus norvegicus	207-215
33316842-10	2021	CONCLUSION: The current example uses the PBPK model to guide dose adjustment of tramadol and to predict the effect of CYP2D6 genetic polymorphisms on DDIs for rational clinical use of tramadol in the future.	Tramadol	184-192	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	118-124
33249277-12	2021	In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose.	Tramadol	117-125	glutamate ionotropic receptor NMDA type subunit 1	Rattus norvegicus	80-83
33249277-12	2021	In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose.	Tramadol	117-125	glutamate ionotropic receptor AMPA type subunit 1	Rattus norvegicus	88-93
33249277-13	2021	These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.	Tramadol	67-75	neurochondrin	Rattus norvegicus	178-184
33249277-13	2021	These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.	Tramadol	67-75	glutamate ionotropic receptor NMDA type subunit 1	Rattus norvegicus	204-207
33249277-13	2021	These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.	Tramadol	67-75	glutamate ionotropic receptor AMPA type subunit 1	Rattus norvegicus	212-217
33249277-13	2021	These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.	Tramadol	138-146	neurochondrin	Rattus norvegicus	178-184
33249277-13	2021	These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.	Tramadol	138-146	glutamate ionotropic receptor NMDA type subunit 1	Rattus norvegicus	204-207
32488232-0	2020	The Associations Between CYP2D6*10 C188T Polymorphism and Pharmacokinetics and Clinical Outcomes of Tramadol: A Systematic Review and Meta-analysis.	Tramadol	100-108	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	25-31
32488232-2	2020	Recently, a number of studies have explored the associations of the CYP2D6*10 C188T polymorphism with pharmacokinetic and clinical outcomes of tramadol.	Tramadol	143-151	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	68-74
32488232-5	2020	METHODS: PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies that explored the influence of the CYP2D6*10 C188T polymorphism on clinical outcomes of tramadol through April 2019.	Tramadol	181-189	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	128-134
32488232-9	2020	Significant associations were found between CYP2D6*10 C188T mutation and longer serum tramadol half-lives, larger AUC0- , and the slower clearance rate of tramadol.	Tramadol	86-94	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	44-50
32488232-9	2020	Significant associations were found between CYP2D6*10 C188T mutation and longer serum tramadol half-lives, larger AUC0- , and the slower clearance rate of tramadol.	Tramadol	155-163	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	44-50
32488232-10	2020	In addition, we also found that CYP2D6*10 C188T had effects on the pharmacokinetic parameters of the metabolite of tramadol, O-desmethyltramadol, by sensitive analysis.	Tramadol	115-123	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	32-38
32488232-11	2020	Furthermore, CYP2D6*10 C188T polymorphism was associated with higher visual analog scale score, loading dose, and total consumption of tramadol.	Tramadol	135-143	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	13-19
32488232-13	2020	CONCLUSIONS: CYP2D6*10 C188T polymorphism had a significant influence on tramadol pharmacokinetics and analgesic effect, but there was insufficient evidence to demonstrate that this polymorphism was associated with incidence of nausea and vomiting.	Tramadol	73-81	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	13-19
33276071-2	2021	AIM: This study aimed to evaluate the protective effect of vitamin C (Vit C) in cerebrocortical toxicity mediated by tramadol in rats using biochemical and histological parameters.	Tramadol	117-125	vitrin	Rattus norvegicus	70-73
33276071-7	2021	RESULTS: Tramadol administration leads to a significant elevation of MDA, NO levels and a significant decrease in antioxidants parameters (CAT, SOD and GSH) in the tissues of cerebral cortices in rats which were directly proportional to the dose of tramadol.	Tramadol	9-17	catalase	Rattus norvegicus	139-142
33316842-0	2021	Physiologically based pharmacokinetic modeling of tramadol to inform dose adjustment and drug-drug interactions according to CYP2D6 phenotypes.	Tramadol	50-58	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	125-131
33316842-3	2021	METHODS: Plasma concentrations of tramadol and M1 were used to adjust the turnover frequency (Kcat ) of CYP2D6 for phenotype populations with different CYP2D6 genotypes.	Tramadol	34-42	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	104-110
33316842-3	2021	METHODS: Plasma concentrations of tramadol and M1 were used to adjust the turnover frequency (Kcat ) of CYP2D6 for phenotype populations with different CYP2D6 genotypes.	Tramadol	34-42	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	152-158
33316842-5	2021	The validated models were then used to support dose adjustment in different CYP2D6 phenotypes and to predict the extent of CYP2D6-mediated DDIs when tramadol was co-administered with paroxetine or duloxetine.	Tramadol	149-157	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	123-129
33316842-6	2021	RESULTS: The PBPK models we built accurately describe tramadol and M1 exposure in the population with different CYP2D6 phenotypes.	Tramadol	54-62	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	112-118
33387367-2	2021	Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone and methadone).	Tramadol	67-75	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	50-56
33387367-6	2021	We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone and methadone and for OPRM1 and COMT for clinical use.	Tramadol	106-114	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	54-60
32921297-0	2021	The effects of cytochrome P450 2D6 inhibitors on a high-dose tramadol taper for medically supervised opioid withdrawal: a retrospective chart review.	Tramadol	61-69	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	15-34
32921297-2	2021	Tramadol is metabolized by CYP2D6 to an active metabolite with significantly more pharmacologic activity compared to the parent compound.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	27-33
32921297-3	2021	OBJECTIVES: The objective of this study is to evaluate the effects of CYP2D6 inhibitors on patient response to a tramadol taper for medically supervised opioid withdrawal.	Tramadol	113-121	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	70-76
32440822-5	2020	Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2"-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities.	Tramadol	0-12	catalase	Rattus norvegicus	217-220
33217744-2	2020	Stability of Extemporaneous Oral Tramadol, Fluoxetine, and Doxycycline Suspensions in SyrSpend SF PH4.	Tramadol	33-41	prolyl 4-hydroxylase, transmembrane	Homo sapiens	98-101
33142187-8	2020	Generally, the TRA concentration was higher than the metabolites concentrations but depended on the CYP2D6 phenotype.	Tramadol	15-18	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	100-106
32639294-3	2020	The objective of this study was to compare tramadol abuse patients and healthy controls regarding free testosterone and prolactin levels and semen analysis.	Tramadol	43-51	prolactin	Homo sapiens	120-129
32443139-0	2020	CYP2D6 Basic Genotyping of Patients with Chronic Pain Receiving Tramadol or Codeine.	Tramadol	64-72	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
32443139-2	2020	OBJECTIVE: To assess CYP2D6 genotype prevalence in chronic pain patients treated with tramadol or codeine.	Tramadol	86-94	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	21-27
32904295-9	2020	PGF2alpha induced the release and the mRNA expression of OPG, which tramadol significantly enhanced.	Tramadol	68-76	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	57-60
32904295-11	2020	In addition, naloxone, a MOR antagonist, suppressed the enhancement by tramadol or morphine of the PGF2alpha-induced OPG synthesis.	Tramadol	71-79	opioid receptor, mu 1	Mus musculus	25-28
32904295-11	2020	In addition, naloxone, a MOR antagonist, suppressed the enhancement by tramadol or morphine of the PGF2alpha-induced OPG synthesis.	Tramadol	71-79	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	117-120
32904295-12	2020	Tramadol upregulated the phosphorylation of SAPK/JNK and p38 MAPK stimulated by PGF2alpha but not that of p44/p42 MAPK or myosin phosphatase targeting protein (MYPT), a substrate of Rho-kinase.	Tramadol	0-8	mitogen-activated protein kinase 8	Mus musculus	49-52
32904295-12	2020	Tramadol upregulated the phosphorylation of SAPK/JNK and p38 MAPK stimulated by PGF2alpha but not that of p44/p42 MAPK or myosin phosphatase targeting protein (MYPT), a substrate of Rho-kinase.	Tramadol	0-8	mitogen-activated protein kinase 14	Mus musculus	57-65
32904295-12	2020	Tramadol upregulated the phosphorylation of SAPK/JNK and p38 MAPK stimulated by PGF2alpha but not that of p44/p42 MAPK or myosin phosphatase targeting protein (MYPT), a substrate of Rho-kinase.	Tramadol	0-8	Rho-associated coiled-coil containing protein kinase 2	Mus musculus	182-192
32904295-13	2020	The inhibitors of both p38 MAPK and SAPK/JNK, SB203580 and SP600125, respectively, reduced the tramadol amplification of OPG release stimulated by PGF2alpha.	Tramadol	95-103	mitogen-activated protein kinase 14	Mus musculus	23-31
32904295-13	2020	The inhibitors of both p38 MAPK and SAPK/JNK, SB203580 and SP600125, respectively, reduced the tramadol amplification of OPG release stimulated by PGF2alpha.	Tramadol	95-103	mitogen-activated protein kinase 8	Mus musculus	41-44
32904295-13	2020	The inhibitors of both p38 MAPK and SAPK/JNK, SB203580 and SP600125, respectively, reduced the tramadol amplification of OPG release stimulated by PGF2alpha.	Tramadol	95-103	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	121-124
32904295-14	2020	The present results strongly suggest that tramadol enhances the synthesis of OPG stimulated by PGF2alpha through MOR in osteoblasts, and that the amplifying effect is exerted at upstream of p38 MAPK and SAPK/JNK but downstream of Rho-kinase.	Tramadol	42-50	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	77-80
32904295-14	2020	The present results strongly suggest that tramadol enhances the synthesis of OPG stimulated by PGF2alpha through MOR in osteoblasts, and that the amplifying effect is exerted at upstream of p38 MAPK and SAPK/JNK but downstream of Rho-kinase.	Tramadol	42-50	opioid receptor, mu 1	Mus musculus	113-116
32904295-14	2020	The present results strongly suggest that tramadol enhances the synthesis of OPG stimulated by PGF2alpha through MOR in osteoblasts, and that the amplifying effect is exerted at upstream of p38 MAPK and SAPK/JNK but downstream of Rho-kinase.	Tramadol	42-50	mitogen-activated protein kinase 8	Mus musculus	208-211
32904295-14	2020	The present results strongly suggest that tramadol enhances the synthesis of OPG stimulated by PGF2alpha through MOR in osteoblasts, and that the amplifying effect is exerted at upstream of p38 MAPK and SAPK/JNK but downstream of Rho-kinase.	Tramadol	42-50	Rho-associated coiled-coil containing protein kinase 2	Mus musculus	230-240
32378056-4	2020	At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 muM for 48 h).	Tramadol	112-120	annexin A5	Rattus norvegicus	46-55
32378056-6	2020	Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF.	Tramadol	25-33	caspase 3	Rattus norvegicus	111-126
32378056-6	2020	Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF.	Tramadol	25-33	glial cell derived neurotrophic factor	Rattus norvegicus	176-180
32649306-0	2020	Stability of Extemporaneous Oral Tramadol, Fluoxetine, and Doxycycline Suspensions in SyrSpend SF pH4.	Tramadol	33-41	prolyl 4-hydroxylase, transmembrane	Homo sapiens	98-101
33217744-1	2020	2020; 24(4): 327 Stability of Extemporaneous Oral Tramadol, Fluoxetine, and Doxycycline Suspensions in SyrSpend SF PH4.	Tramadol	50-58	prolyl 4-hydroxylase, transmembrane	Homo sapiens	115-118
32904295-0	2020	Tramadol enhances PGF2alpha-stimulated osteoprotegerin synthesis in osteoblasts.	Tramadol	0-8	tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin)	Mus musculus	39-54
32361903-0	2020	Clinically significant drug-drug interactions between tramadol and CYP3A4 inhibitors: disproportionality analysis in VigiBase  and hypothesis on the underlying mechanism.	Tramadol	54-62	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	67-73
32681776-0	2020	Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms.	Tramadol	14-22	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
32538291-0	2020	Involvement of CYP2D6 and CYP2B6 on tramadol pharmacokinetics.	Tramadol	36-44	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	15-21
32538291-0	2020	Involvement of CYP2D6 and CYP2B6 on tramadol pharmacokinetics.	Tramadol	36-44	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	26-32
32538291-3	2020	CYP2D6 intermediate metabolizers (n = 6) showed higher tramadol plasma concentrations and lower clearance compared with normal and ultrarapid metabolizers.	Tramadol	55-63	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
32538291-4	2020	CYP2B6 G516T T/T (n = 2) genotype was also associated to higher tramadol plasma levels.	Tramadol	64-72	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	0-6
32538291-7	2020	The correlation of CYP2B6 genotype with higher tramadol concentrations is remarkable since its influence on its elimination is also relevant and has been less studied to date.	Tramadol	47-55	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	19-25
32513525-12	2020	After IN administration, tramadol was rapidly absorbed into the systemic circulation, reaching its maximum concentration (range 74.74-200.29 ng mL-1) within 30-60 minutes, it then decreased rapidly and was detectable in plasma at least up to 2 hours after treatment in all dogs.	Tramadol	25-33	L1 cell adhesion molecule	Mus musculus	144-148
32598307-0	2020	Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms.	Tramadol	14-22	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
32598307-1	2020	Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning.	Tramadol	43-51	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	76-82
32598307-1	2020	Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning.	Tramadol	166-174	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	146-152
32681776-1	2020	Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning.	Tramadol	43-51	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	76-82
32681776-1	2020	Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning.	Tramadol	166-174	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	146-152
32442101-7	2020	CYP2D6 enzymes metabolize codeine and tramadol.	Tramadol	38-46	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
32214840-2	2020	We used a large sample of patients to study associations between CYP2D6 phenotypes and estimated CYP2D6 enzymatic activity scores with pain control and adverse reactions related to codeine and tramadol use.	Tramadol	193-201	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	65-71
31613803-11	2020	In the demethylation assay, the O-demethylations of tramadol and NDT by CYP2D6 were (-)-form-selective.	Tramadol	52-60	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	72-78
31613803-13	2020	Although CYP2D6 contributed to the stereoselective demethylation of tramadol, remarkable differences between (+)- and (-)-ODT were not observed in the plasma of the cancer patients.	Tramadol	68-76	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	9-15
32782734-8	2020	In addition, tramadol induced a significant decrease in Bcl-2 gene expression, and increase in Bax gene expression.	Tramadol	13-21	BCL2, apoptosis regulator	Rattus norvegicus	56-61
32782734-8	2020	In addition, tramadol induced a significant decrease in Bcl-2 gene expression, and increase in Bax gene expression.	Tramadol	13-21	BCL2 associated X, apoptosis regulator	Rattus norvegicus	95-98
32214840-2	2020	We used a large sample of patients to study associations between CYP2D6 phenotypes and estimated CYP2D6 enzymatic activity scores with pain control and adverse reactions related to codeine and tramadol use.	Tramadol	193-201	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	97-103
30851501-18	2019	CONCLUSION: Ultrasound-guided ESP block reduced postoperative tramadol consumption and pain scores more effectively than OSTAP block after laparoscopic cholecystectomy surgery.	Tramadol	62-70	protein tyrosine phosphatase receptor type V, pseudogene	Homo sapiens	30-33
31618080-6	2020	The results indicated that Sub-chronic administration of Tramadol resulted in impaired liver functions, increased oxidative stress parameters with decreased antioxidant capacity of liver tissues, severe hepatocellular damage (hydropic degeneration, steatosis and apoptosis) and strong immunoexpression to TNF[Formula: see text] and Caspase 3.	Tramadol	57-65	tumor necrosis factor	Rattus norvegicus	305-308
31618080-6	2020	The results indicated that Sub-chronic administration of Tramadol resulted in impaired liver functions, increased oxidative stress parameters with decreased antioxidant capacity of liver tissues, severe hepatocellular damage (hydropic degeneration, steatosis and apoptosis) and strong immunoexpression to TNF[Formula: see text] and Caspase 3.	Tramadol	57-65	caspase 3	Rattus norvegicus	332-341
31839727-12	2020	What happened: The hypoglycaemia was caused by inappropriate stimulation of insulin secretion in a patient intoxicated with tramadol.	Tramadol	124-132	insulin	Homo sapiens	76-83
31839727-14	2020	Main lesson: To our knowledge, we are the first to document a significant rise in endogenous insulin production in a hypoglycaemic patient presenting with tramadol intoxication.	Tramadol	155-163	insulin	Homo sapiens	93-100
30971809-1	2020	Phase I tramadol metabolism requires cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) to form O-desmethyltramadol (M1).	Tramadol	8-16	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	37-89
30971809-1	2020	Phase I tramadol metabolism requires cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) to form O-desmethyltramadol (M1).	Tramadol	8-16	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	91-97
31924115-6	2020	Tramadol treated groups showed degenerative changes in dentate gyrus (DG) granule cells, pyramidal neurons of CA1and CA3 fields in the form of electron-dense or rarified cytoplasm, dilated rER and mitochondrial changes.	Tramadol	0-8	carbonic anhydrase 1	Mus musculus	110-113
31924115-6	2020	Tramadol treated groups showed degenerative changes in dentate gyrus (DG) granule cells, pyramidal neurons of CA1and CA3 fields in the form of electron-dense or rarified cytoplasm, dilated rER and mitochondrial changes.	Tramadol	0-8	carbonic anhydrase 3	Mus musculus	117-120
31591020-12	2019	The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.	Tramadol	26-34	5-hydroxytryptamine receptor 2B	Homo sapiens	122-137
31591020-12	2019	The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.	Tramadol	26-34	transient receptor potential cation channel subfamily V member 1	Homo sapiens	142-148
31597043-1	2019	Genetic variants in the hepatic uptake transporter OCT1, observed in 9% of Europeans and White Americans, are known to affect pharmacokinetics and efficacy of tramadol, morphine, and codeine.	Tramadol	159-167	solute carrier family 22 member 1	Homo sapiens	51-55
31685008-7	2019	Male sex (OR 1.28 in tramadol, OR 1.13 in stronger opioids) and comorbidities with depression (OR 1.05, 1.46), low back pain (OR 1.13, 1.30), intervertebral disc disorder (OR 1.11, 1.40), and spinal stenosis (OR 1.27, 1.55) were the factors for the early use of tramadol or stronger opioids in knee OA patients.	Tramadol	21-29	olfactory receptor family 10 subfamily J member 5	Homo sapiens	10-17
31969823-7	2019	Her CYP2D6 genotype was *5/*17, consistent with intermediate metabolism, making opioid drugs reliant on CYP2D6 activation, such as tramadol and hydrocodone, relatively ineffective in this patient.	Tramadol	131-139	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	4-10
31969823-7	2019	Her CYP2D6 genotype was *5/*17, consistent with intermediate metabolism, making opioid drugs reliant on CYP2D6 activation, such as tramadol and hydrocodone, relatively ineffective in this patient.	Tramadol	131-139	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	104-110
32612076-6	2020	Similar to ACAP, the combination of tramadol and probenecid or valproate, which has the potential to inhibit uridine 5"-diphosphate (UDP)-glucuronosyltransferase (UGT), also suppressed the CFA-induced mechanical allodynia and slowed gastrointestinal transit.	Tramadol	36-44	solute carrier family 35 (UDP-galactose transporter), member A2	Mus musculus	163-166
31653394-6	2020	Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity.	Tramadol	42-50	solute carrier family 6 member 4	Homo sapiens	36-40
32486995-8	2020	Buprenorphine, fentanyl, hydromorphone, morphine, naloxone und tapentadol are drugs with a high first-pass effect, while the bioavailability of methadone, oxycodone and tramadol is > 70 %.	Tramadol	169-177	collagen type XIV alpha 1 chain	Homo sapiens	59-62
32461718-11	2019	Additionally, significant decrease in serum testosterone level and increase in serum prolactin level as tramadol daily dose and duration increased was found.	Tramadol	104-112	prolactin	Homo sapiens	85-94
31744222-0	2019	Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling.	Tramadol	48-56	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	28-34
31744222-2	2019	O-desmethyltramadol (M1), the major active metabolite of tramadol, is produced by CYP2D6.	Tramadol	11-19	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	82-88
31744222-3	2019	A physiologically-based pharmacokinetic model was developed to predict changes in time-concentration profiles for tramadol and M1 according to dosage and CYP2D6 genotypes in the Korean population.	Tramadol	114-122	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	154-160
31535328-1	2019	INTRODUCTION: In 2016, the orally administered fixed-dose combination of dexketoprofen 25 mg and tramadol 75 mg (DKP/TRAM FDC) was approved in Europe for short-term treatment of moderate-to-severe acute pain, an indication that encompasses a wide range of post-operative and non-surgical painful conditions.	Tramadol	97-105	translocation associated membrane protein 1	Homo sapiens	117-121
31005596-3	2019	Tramadol labeling indicates cytochrome P450 (CYP) isozyme 2D6 ultrarapid metabolizer can produce dangerous (+)-M1 levels, and CYP2D6 poor metabolizers insufficient (+)-M1 for analgesia.	Tramadol	0-8	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	28-43
31518605-13	2019	SIGNIFICANCE: Spinal NKCC1 cotransporter and peptidergic peripheral afferents seem to be important for the analgesic and antiedematogenic effects of tramadol, as well as mu-opioid receptor.	Tramadol	149-157	solute carrier family 12 member 2	Rattus norvegicus	21-26
31005596-3	2019	Tramadol labeling indicates cytochrome P450 (CYP) isozyme 2D6 ultrarapid metabolizer can produce dangerous (+)-M1 levels, and CYP2D6 poor metabolizers insufficient (+)-M1 for analgesia.	Tramadol	0-8	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	45-48
31005596-7	2019	In trial B, CYP inhibition significantly depressed tramadol steady-state (+)-M1, reduced its adverse events, and led to insignificant analgesia comparable with placebo.	Tramadol	51-59	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	12-15
30778911-3	2019	Tramadol is a commonly used analgesic metabolised mainly via CYP2D6 to its active metabolite, O-desmethyltramadol.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	61-67
30872390-9	2019	The proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta (IL-1beta) were found to be reduced, whereas the anti-inflammatory cytokine IL-10 was found to be elevated in tramadol-treated groups.	Tramadol	190-198	interleukin 10	Rattus norvegicus	156-161
31486733-2	2019	Genetic variations associated with drug effectiveness or adverse reactions (amitriptyline/nortriptyline/codeine/oxycodone/tramadol-CYP2D6, amitriptyline-CYP2C19, carbamazepine-HLA-A, carbamazepine/oxcarbazepine-HLA-B) can be used to guide chronic pain management.	Tramadol	122-130	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	131-137
30670877-1	2019	PURPOSE: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia.	Tramadol	41-49	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	9-15
30824817-6	2019	These data identify UGT2B7 as a potentially significant explanatory marker for T:M1 variability in a population of tramadol-exposed individuals of Finnish ancestry.	Tramadol	115-123	UDP glucuronosyltransferase family 2 member B7	Homo sapiens	20-26
31051223-0	2019	mu-Opioid receptor in the CA1 involves in tramadol and morphine cross state-dependent memory.	Tramadol	42-50	carbonic anhydrase 1	Rattus norvegicus	26-29
31051223-5	2019	In addition, the pre-test administration of morphine (1 mug/rat, intra-CA1) also reversed memory impairment induced by pre-train tramadol administration.	Tramadol	129-137	carbonic anhydrase 1	Rattus norvegicus	71-74
31051223-6	2019	Although, pre-train morphine administration (1 mug/rat, intra-CA1), induced memory impairment reversed by pre-test tramadol administration (1 mug/rat, intra-CA1).	Tramadol	115-123	carbonic anhydrase 1	Rattus norvegicus	62-65
31051223-6	2019	Although, pre-train morphine administration (1 mug/rat, intra-CA1), induced memory impairment reversed by pre-test tramadol administration (1 mug/rat, intra-CA1).	Tramadol	115-123	carbonic anhydrase 1	Rattus norvegicus	157-160
31051223-9	2019	The results of the study suggested that intra-CA1 tramadol administration induced memory impairment, improved by pre-test administration of either tramadol or morphine (MOR agonist).	Tramadol	50-58	carbonic anhydrase 1	Rattus norvegicus	46-49
31051223-9	2019	The results of the study suggested that intra-CA1 tramadol administration induced memory impairment, improved by pre-test administration of either tramadol or morphine (MOR agonist).	Tramadol	147-155	carbonic anhydrase 1	Rattus norvegicus	46-49
31004280-4	2019	Tramadol has modulatory effects on several mediators involved in pain signaling, such as voltage-gated sodium ion channels, transient receptor potential V1 channels, glutamate receptors, alpha2-adrenoceptors, adenosine receptors, and mechanisms involving substance P, calcitonin gene-related peptide, prostaglandin E2, and proinflammatory cytokines.	Tramadol	0-8	tachykinin precursor 1	Homo sapiens	255-266
31201197-0	2019	Correction: Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study).	Tramadol	12-20	translocation associated membrane protein 1	Homo sapiens	36-40
30644574-7	2019	The calibration linear range for tramadol hydrochloride, alprazolam, diazepam, chlorpheniramine maleate, diphenylhydramine and paracetamol was 5-500 ng mL-1 .	Tramadol	33-55	L1 cell adhesion molecule	Mus musculus	152-156
31038218-12	2019	CONCLUSION: This study demonstrated a clinically relevant decrease in the efficacy of tramadol when used for pain control in patients receiving a strong CYP2D6 inhibitor.	Tramadol	86-94	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	153-159
31213765-0	2019	Population pharmacokinetic analysis of tramadol and O-desmethyltramadol with genetic polymorphism of CYP2D6.	Tramadol	39-47	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	101-107
31213765-3	2019	Tramadol is metabolized to M1 mainly by the cytochrome P450 (CYP) 2D6 enzyme, and to other metabolites by CYP3A4 and CYP2B6.	Tramadol	0-8	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	117-123
31213765-11	2019	Genetic polymorphisms of CYP2D6 correlated with the clearance of tramadol, and clearance from the central compartment to the metabolite compartment.	Tramadol	65-73	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	25-31
30675632-10	2019	SR-TRAM had the highest mean doses and durations, followed by immediate release formulations of tramadol (IR-TRAM) and COMB.	Tramadol	96-104	translocation associated membrane protein 1	Homo sapiens	109-113
30507617-0	2019	Supervised Classification of CYP2D6 Genotype and Metabolizer Phenotype With Postmortem Tramadol-Exposed Finns.	Tramadol	87-95	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	29-35
30784356-1	2019	Background: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions.	Tramadol	12-20	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	52-58
30782886-0	2019	Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study).	Tramadol	0-8	translocation associated membrane protein 1	Homo sapiens	24-28
30508735-6	2019	Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-alpha and IL-6) and expression of NF-kappaB, iNOS, TNF-alpha and IL-6 in the cerebrum of rats.	Tramadol	0-8	tumor necrosis factor	Rattus norvegicus	92-101
30508735-6	2019	Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-alpha and IL-6) and expression of NF-kappaB, iNOS, TNF-alpha and IL-6 in the cerebrum of rats.	Tramadol	0-8	interleukin 6	Rattus norvegicus	106-110
30508735-6	2019	Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-alpha and IL-6) and expression of NF-kappaB, iNOS, TNF-alpha and IL-6 in the cerebrum of rats.	Tramadol	0-8	nitric oxide synthase 2	Rattus norvegicus	141-145
30508735-6	2019	Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-alpha and IL-6) and expression of NF-kappaB, iNOS, TNF-alpha and IL-6 in the cerebrum of rats.	Tramadol	0-8	tumor necrosis factor	Rattus norvegicus	147-156
30508735-6	2019	Tramadol administration for 8 weeks resulted in increased serum pro-inflammatory cytokines (TNF-alpha and IL-6) and expression of NF-kappaB, iNOS, TNF-alpha and IL-6 in the cerebrum of rats.	Tramadol	0-8	interleukin 6	Rattus norvegicus	161-165
30508735-7	2019	Monoamine neurotransmitters, 8-oxo-7,8-dihydro-2"-deoxyguanosine, and gene and protein expression levels of p53 and Bax were significantly increased in the cerebrum of tramadol-induced rats.	Tramadol	168-176	Wistar clone pR53P1 p53 pseudogene	Rattus norvegicus	108-111
30508735-7	2019	Monoamine neurotransmitters, 8-oxo-7,8-dihydro-2"-deoxyguanosine, and gene and protein expression levels of p53 and Bax were significantly increased in the cerebrum of tramadol-induced rats.	Tramadol	168-176	BCL2 associated X, apoptosis regulator	Rattus norvegicus	116-119
30508735-8	2019	In contrast, chronic tramadol administration down-regulated Bcl-2 both gene and protein expression in the cerebrum of rats.	Tramadol	21-29	BCL2, apoptosis regulator	Rattus norvegicus	60-65
30632799-0	2019	Tramadol induces changes in Delta-FosB, micro-opioid receptor, and p-CREB level in the nucleus accumbens and prefrontal cortex of male Wistar rat.	Tramadol	0-8	cAMP responsive element binding protein 1	Rattus norvegicus	69-73
30317449-0	2019	Interleukin-1beta in synergism gabapentin with tramadol in murine model of diabetic neuropathy.	Tramadol	47-55	interleukin 1 beta	Mus musculus	0-17
30317449-2	2019	The aim of this study was to evaluate the role of the biomarker interleukin-1beta (IL-1ss) in the pharmacological interaction of gabapentin with tramadol in a model of diabetic neuropathic pain.	Tramadol	145-153	interleukin 1 beta	Mus musculus	64-81
30317449-9	2019	The combination of gabapentin with tramadol reversed the increased concentration of IL-1beta induced by STZ in diabetic neuropathic mice.	Tramadol	35-43	interleukin 1 beta	Mus musculus	84-92
30632799-11	2019	RESULTS: In the NAC, acute tramadol exposure increases the levels of MOR and p-CREB.	Tramadol	27-35	cAMP responsive element binding protein 1	Rattus norvegicus	79-83
30632799-12	2019	Moreover, chronic tramadol administration in this region results in elevated levels of MOR, DeltaFosB and p-CREB compared with saline-treated rats.	Tramadol	18-26	cAMP responsive element binding protein 1	Rattus norvegicus	108-112
30632799-13	2019	The levels of MOR and p-CREB in the PFC increased in both acute and chronic tramadol exposure.	Tramadol	76-84	cAMP responsive element binding protein 1	Rattus norvegicus	24-28
30632799-16	2019	CONCLUSION: We concluded that both CREB and DeltaFosB played a role in tramadol dependence.	Tramadol	71-79	cAMP responsive element binding protein 1	Rattus norvegicus	35-39
30113702-1	2018	We previously showed that (+)-tramadol is metabolized in dog liver to (+)-M1 exclusively by CYP2D15 and to (+)-M2 by multiple CYPs, but primarily CYP2B11.	Tramadol	26-38	cytochrome P450 2D15	Canis lupus familiaris	92-99
31822353-8	2019	Mean postoperative tramadol consumption was 100+-19.2mg in Group ESP, while it was 143+-18.6mg in Group Control (p<0.001).	Tramadol	19-27	protein tyrosine phosphatase receptor type V, pseudogene	Homo sapiens	65-68
30346535-1	2019	Background: Tramadol, a centrally acting analgesic drug, has relatively high affinity to serotonin transporter and norepinephrine transporter in addition to mu-opioid receptor.	Tramadol	12-20	sodium-dependent serotonin transporter	Macaca fascicularis	89-110
30346535-1	2019	Background: Tramadol, a centrally acting analgesic drug, has relatively high affinity to serotonin transporter and norepinephrine transporter in addition to mu-opioid receptor.	Tramadol	12-20	mu-type opioid receptor	Macaca fascicularis	157-175
30346535-6	2019	Results: Tramadol occupied similarly both serotonin transporter (40%-72%) and norepinephrine transporter (7%-73%) in a dose-dependent manner.	Tramadol	9-17	sodium-dependent serotonin transporter	Macaca fascicularis	42-63
30346535-8	2019	Conclusions: Both serotonin transporter and norepinephrine transporter of in vivo brain were blocked at &gt;70% at a clinically relevant high dose of tramadol.	Tramadol	150-158	sodium-dependent serotonin transporter	Macaca fascicularis	18-39
30346535-9	2019	This study suggests tramadol has potential antidepressant effects through the inhibition of serotonin transporter and norepinephrine transporter in the brain.	Tramadol	20-28	sodium-dependent serotonin transporter	Macaca fascicularis	92-113
30113702-1	2018	We previously showed that (+)-tramadol is metabolized in dog liver to (+)-M1 exclusively by CYP2D15 and to (+)-M2 by multiple CYPs, but primarily CYP2B11.	Tramadol	26-38	cytochrome P450 2B11	Canis lupus familiaris	146-153
30051214-0	2018	Impact of CYP genotype and inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.	Tramadol	80-88	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	10-13
30051214-6	2018	The plasma concentration of O-desmethyltramadol and its ratio to tramadol were lower in the CYP2D6 intermediate and poor metabolizer (IM + PM) group than in the normal metabolizer (NM) group (P = 0.002 and P = 0.023).	Tramadol	39-47	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	92-98
30051214-7	2018	The plasma concentration of N-desmethyltramadol and its ratio to tramadol were higher in the CYP2D6 IM + PM group than in the NM group (P = 0.001 and P = 0.001).	Tramadol	39-47	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	93-99
30051214-2	2018	This study aimed to evaluate the impacts of cytochrome P450 (CYP) genotype and serum inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.	Tramadol	138-146	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	61-64
30051214-9	2018	The serum IL-6 and CRP levels were inversely correlated with the plasma concentration ratios of N-desmethyltramadol to tramadol and of N,O-didesmethyltramadol to O-desmethyltramadol.	Tramadol	107-115	interleukin 6	Homo sapiens	10-14
30051214-2	2018	This study aimed to evaluate the impacts of cytochrome P450 (CYP) genotype and serum inflammatory markers on the plasma concentrations of tramadol and its demethylated metabolites and drug tolerability in cancer patients.	Tramadol	138-146	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	44-59
30051214-9	2018	The serum IL-6 and CRP levels were inversely correlated with the plasma concentration ratios of N-desmethyltramadol to tramadol and of N,O-didesmethyltramadol to O-desmethyltramadol.	Tramadol	107-115	C-reactive protein	Homo sapiens	19-22
30117229-13	2018	Tramadol had a C50, TRAM of 0.07 (95%CI 0.048, 1.07) mg/L with a t1/2 keo,TRAM 1.78 hour (95%CI 1.06, 1.96).	Tramadol	0-8	translocation associated membrane protein 1	Homo sapiens	20-24
30051214-10	2018	The serum IL-6 level was associated with the treatment duration of oral tramadol.	Tramadol	72-80	interleukin 6	Homo sapiens	10-14
30051214-11	2018	CONCLUSIONS: The CYP2D6 genotype but not the CYP2B6 and CYP3A5 genotypes affected the plasma concentrations of O- and N-desmethyltramadol through alteration of the tramadol metabolic pathway.	Tramadol	129-137	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	17-23
30051214-12	2018	The serum IL-6 level was associated with N-demethylation activity and tramadol tolerability.	Tramadol	70-78	interleukin 6	Homo sapiens	10-14
30293115-0	2018	Letter to Editor concerning "Comparative study of the efficacy of transdermal buprenorphine patches and prolonged-release tramadol tablets for postoperative pain control after spinal fusion surgery: a prospective, randomized controlled non-inferiority trial" by Kim HJ, Ahn HS, Nam Y, Chang BS, Lee CK, Yeom JS (2017) Eur Spine J 26:2961-2968.	Tramadol	122-130	SH3 and cysteine rich domain 3	Homo sapiens	278-281
30425549-2	2018	Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity.	Tramadol	9-17	peptidylprolyl isomerase G	Homo sapiens	51-54
30425549-2	2018	Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity.	Tramadol	9-17	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	67-73
29994939-3	2018	The recent pharmacogenetics studies revealed an association of the organic cation transporter 1 (OCT1) and ATP-binding cassette C3 (ABCC3) polymorphisms with morphine-related adverse effects, an effect of polymorphisms in cytochrome P450 gene CYP2D6 on the analgesic efficacy of tramadol and no effect of CYP2C8 and CYP2C9 variants on efficacy of piroxicam.	Tramadol	279-287	solute carrier family 22 member 1	Homo sapiens	67-95
29994939-3	2018	The recent pharmacogenetics studies revealed an association of the organic cation transporter 1 (OCT1) and ATP-binding cassette C3 (ABCC3) polymorphisms with morphine-related adverse effects, an effect of polymorphisms in cytochrome P450 gene CYP2D6 on the analgesic efficacy of tramadol and no effect of CYP2C8 and CYP2C9 variants on efficacy of piroxicam.	Tramadol	279-287	solute carrier family 22 member 1	Homo sapiens	97-101
29994939-3	2018	The recent pharmacogenetics studies revealed an association of the organic cation transporter 1 (OCT1) and ATP-binding cassette C3 (ABCC3) polymorphisms with morphine-related adverse effects, an effect of polymorphisms in cytochrome P450 gene CYP2D6 on the analgesic efficacy of tramadol and no effect of CYP2C8 and CYP2C9 variants on efficacy of piroxicam.	Tramadol	279-287	ATP binding cassette subfamily C member 3	Homo sapiens	132-137
30248201-6	2018	Such PK differences among individuals are known not only for codeine and tramadol through pharmacogenetic variants of CYP2D6 but also for non-CYP2D6 substrate opioids including oxycodone, indicating difficulties of eliminating PK uncertainty by simply replacing an opioid with another.	Tramadol	73-81	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	118-124
30117229-13	2018	Tramadol had a C50, TRAM of 0.07 (95%CI 0.048, 1.07) mg/L with a t1/2 keo,TRAM 1.78 hour (95%CI 1.06, 1.96).	Tramadol	0-8	translocation associated membrane protein 1	Homo sapiens	74-80
30149704-6	2018	This is partly due to two positively charged residues, K304 and K315, present in yeast and more broadly in fungi Dus2 that are replaced by E294 and Q305 in human and conserved among animals Dus2.	Tramadol	64-68	tRNA-dihydrouridine(20) synthase (NAD(+))	Saccharomyces cerevisiae S288C	113-117
30070095-0	2018	Assessment of CYP2D6 re-activation after inhibitory effect of MDMA using tramadol as a probe.	Tramadol	73-81	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
30149704-6	2018	This is partly due to two positively charged residues, K304 and K315, present in yeast and more broadly in fungi Dus2 that are replaced by E294 and Q305 in human and conserved among animals Dus2.	Tramadol	64-68	dihydrouridine synthase 2	Homo sapiens	190-194
30110401-6	2018	On the other hand, repeated-dose treatment of rats with tramadol increased the activities of both dimethylnitrosamine N-demethylase I (DMN-dI), and aryl hydrocarbon hydroxylase (AHH) compared to the control group.	Tramadol	56-64	cytochrome P450, family 1, subfamily a, polypeptide 1	Rattus norvegicus	148-176
30110401-6	2018	On the other hand, repeated-dose treatment of rats with tramadol increased the activities of both dimethylnitrosamine N-demethylase I (DMN-dI), and aryl hydrocarbon hydroxylase (AHH) compared to the control group.	Tramadol	56-64	cytochrome P450, family 1, subfamily a, polypeptide 1	Rattus norvegicus	178-181
30110401-7	2018	However, pretreatment of rats with Curcumin and/or Gallic acid prior to administration of tramadol restored the inhibited DMN-dI activity and its protein expression (CYP 2E1) to their normal levels.	Tramadol	90-98	cytochrome P450, family 2, subfamily e, polypeptide 1	Rattus norvegicus	166-173
30110401-8	2018	On the other hand, tramadol inhibited the activity of ethoxycoumarin O-deethylase (ECOD) and suppressed its protein marker expression (CYP2B1/2), whereas Curcumin, Gallic acid and/or their mixture restored such changes to their normal levels.	Tramadol	19-27	cytochrome P450, family 2, subfamily b, polypeptide 12	Rattus norvegicus	135-143
30024967-9	2018	Intrathecal injection of tramadol suppressed synaptic NMDAR expression mainly by changing the synaptic phosphorylation state of NR2B subunit at Tyr1472.	Tramadol	25-33	glutamate receptor, ionotropic, NMDA1 (zeta 1)	Mus musculus	54-59
29916050-6	2018	In studies with human SERT-transfected human HEK293 cells, the synthetic opioids tramadol, meperidine, methadone, tapentadol, and dextromethorphan inhibited SERT, but fentanyl and a number of phenanthrenes including morphine and hydromorphone did not.	Tramadol	81-89	solute carrier family 6 member 4	Homo sapiens	22-26
29916050-6	2018	In studies with human SERT-transfected human HEK293 cells, the synthetic opioids tramadol, meperidine, methadone, tapentadol, and dextromethorphan inhibited SERT, but fentanyl and a number of phenanthrenes including morphine and hydromorphone did not.	Tramadol	81-89	solute carrier family 6 member 4	Homo sapiens	157-161
30024967-10	2018	Extracellular signal-regulated protein kinases 2 (ERK2) activity synchronized with the synaptic expression of NR2BR, which was downregulated by the action of tramadol.	Tramadol	158-166	mitogen-activated protein kinase 1	Mus musculus	0-48
30024967-9	2018	Intrathecal injection of tramadol suppressed synaptic NMDAR expression mainly by changing the synaptic phosphorylation state of NR2B subunit at Tyr1472.	Tramadol	25-33	glutamate receptor, ionotropic, NMDA2B (epsilon 2)	Mus musculus	128-132
30024967-10	2018	Extracellular signal-regulated protein kinases 2 (ERK2) activity synchronized with the synaptic expression of NR2BR, which was downregulated by the action of tramadol.	Tramadol	158-166	mitogen-activated protein kinase 1	Mus musculus	50-54
29997507-0	2018	Tramadol"s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats.	Tramadol	0-8	solute carrier family 6 member 4	Rattus norvegicus	77-98
29027194-2	2018	The aim of this study was to characterize the pediatric predictive performance of the PBPK approach for 10 drugs extensively metabolized by CYP1A2 (theophylline), CYP2C8 (desloratidine, montelukast), CYP2C9 (diclofenac), CYP2C19 (esomeprazole, lansoprazole), CYP2D6 (tramadol), and CYP3A4 (itraconazole, ondansetron, sufentanil).	Tramadol	267-275	cytochrome P450 family 1 subfamily A member 2	Homo sapiens	140-146
29679289-3	2018	Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al.	Tramadol	95-103	carbonic anhydrase 1	Mus musculus	49-52
29679289-3	2018	Previous study revealed that dorsal hippocampus (CA1) plays a crucial role in the retrieval of tramadol-associated memory and that its role depends on the expression of CA1 N-methyl-D-aspartate (NMDA) receptors (Jafari-Sabet et al.	Tramadol	95-103	carbonic anhydrase 1	Mus musculus	169-172
29679289-5	2018	OBJECTIVE: To clarify the exact mechanisms involved, the activation of CA1 nitric oxide (NO) signaling pathway by L-arginine (a nitric oxide precursor) on the interaction between tramadol and MK-801 in memory retrieval was examined.	Tramadol	179-187	carbonic anhydrase 1	Mus musculus	71-74
29679289-14	2018	CONCLUSION: The results strongly propose that activation of CA1 NO signaling pathway has a pivotal role in cross SDL among tramadol and MK-801.	Tramadol	123-131	carbonic anhydrase 1	Mus musculus	60-63
29906478-6	2018	Increased oxidative stress by tramadol and/or nicotine sequentially augmented nuclear factor kappa B and the proinflammatory cytokine tumor necrosis factor alpha with the induction of apoptosis evident by the increased caspase-3 immunoreactivity.	Tramadol	30-38	tumor necrosis factor	Mus musculus	134-161
29906478-6	2018	Increased oxidative stress by tramadol and/or nicotine sequentially augmented nuclear factor kappa B and the proinflammatory cytokine tumor necrosis factor alpha with the induction of apoptosis evident by the increased caspase-3 immunoreactivity.	Tramadol	30-38	caspase 3	Mus musculus	219-228
29997507-7	2018	WAY100,635 (0.3 mg/kg) combined with tramadol (20 mg/kg) significantly reduced sexual activity in SERT+/+ and even stronger in SERT-/- rats.	Tramadol	37-45	solute carrier family 6 member 4	Rattus norvegicus	98-102
29997507-7	2018	WAY100,635 (0.3 mg/kg) combined with tramadol (20 mg/kg) significantly reduced sexual activity in SERT+/+ and even stronger in SERT-/- rats.	Tramadol	37-45	solute carrier family 6 member 4	Rattus norvegicus	127-131
29997507-10	2018	Interestingly, combining tramadol (20 mg/kg), WAY100,635 (0.3 mg/kg) and naloxone (20 mg/kg) led to complete elimination of all sexual activity in both SERT+/+ and SERT-/- rats.	Tramadol	25-33	solute carrier family 6 member 4	Rattus norvegicus	152-156
29997507-10	2018	Interestingly, combining tramadol (20 mg/kg), WAY100,635 (0.3 mg/kg) and naloxone (20 mg/kg) led to complete elimination of all sexual activity in both SERT+/+ and SERT-/- rats.	Tramadol	25-33	solute carrier family 6 member 4	Rattus norvegicus	164-168
29997507-11	2018	These findings suggest that the inhibitory effects of tramadol on male sexual behavior in SERT+/+ rats is mainly, if not exclusively, due to SERT inhibition, with an important role for 5-HT1A receptors, although influence of other systems (e.g., noradrenergic) cannot be excluded.	Tramadol	54-62	solute carrier family 6 member 4	Rattus norvegicus	90-94
29997507-11	2018	These findings suggest that the inhibitory effects of tramadol on male sexual behavior in SERT+/+ rats is mainly, if not exclusively, due to SERT inhibition, with an important role for 5-HT1A receptors, although influence of other systems (e.g., noradrenergic) cannot be excluded.	Tramadol	54-62	solute carrier family 6 member 4	Rattus norvegicus	141-145
28944519-7	2018	Level and trend of monthly utilisation (beta2 : -12.9, beta3 : -1.6) and prevalence of tramadol users (beta2 : -6.4, beta3 : -0.37) significantly reduced after classification.	Tramadol	87-95	potassium calcium-activated channel subfamily M regulatory beta subunit 2	Homo sapiens	103-108
29470767-9	2018	In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P &lt; 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P &lt; 0.05).	Tramadol	3-11	carbonic anhydrase 1	Rattus norvegicus	75-78
29470767-9	2018	In tramadol-treated animals, the dark neurons (DNs) and apoptotic cells in CA1, CA3 and DG increased (P &lt; 0.05), while concurrent intake of crocin decreased the number of DNs and apoptotic cells in these areas (P &lt; 0.05).	Tramadol	3-11	carbonic anhydrase 3	Rattus norvegicus	80-83
29524157-9	2018	Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT were well correlated with the CYP2D6 genotypes.	Tramadol	29-37	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	98-104
29524157-9	2018	Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT were well correlated with the CYP2D6 genotypes.	Tramadol	44-52	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	98-104
28944519-7	2018	Level and trend of monthly utilisation (beta2 : -12.9, beta3 : -1.6) and prevalence of tramadol users (beta2 : -6.4, beta3 : -0.37) significantly reduced after classification.	Tramadol	87-95	eukaryotic translation elongation factor 1 beta 2 pseudogene 2	Homo sapiens	117-122
30104820-3	2018	Codeine and tramadol are prodrugs metabolized by CYP2D6, polymorphisms of which can cause dangerous or even fatal levels of their metabolites, or decrease the level of metabolites to decrease their analgesic effect.	Tramadol	12-20	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	49-55
29555325-0	2018	Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are associated with long term tramadol treatment-induced oxidative damage and hepatotoxicity.	Tramadol	84-92	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	25-44
29555325-0	2018	Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are associated with long term tramadol treatment-induced oxidative damage and hepatotoxicity.	Tramadol	84-92	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	46-52
29555325-1	2018	Our objective was to figure out whether CYP2D6 gene polymorphisms may account for long term tramadol-induced oxidative stress and hepatotoxicity in 60 patients receiving chronic tramadol treatment in Neurology and Rheumatology Outpatients Clinic, Zagazig University Hospitals, Egypt.	Tramadol	92-100	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	40-46
29555325-2	2018	As expected, CYP2D6*1 allele (wild type) frequency was significantly greater than CYP2D6*DUP, CYP2D6*4 and CYP2D6*10 alleles in both chronically tramadol-treated and control groups.	Tramadol	145-153	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	13-19
29555325-2	2018	As expected, CYP2D6*1 allele (wild type) frequency was significantly greater than CYP2D6*DUP, CYP2D6*4 and CYP2D6*10 alleles in both chronically tramadol-treated and control groups.	Tramadol	145-153	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	82-88
29555325-2	2018	As expected, CYP2D6*1 allele (wild type) frequency was significantly greater than CYP2D6*DUP, CYP2D6*4 and CYP2D6*10 alleles in both chronically tramadol-treated and control groups.	Tramadol	145-153	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	82-88
29555325-2	2018	As expected, CYP2D6*1 allele (wild type) frequency was significantly greater than CYP2D6*DUP, CYP2D6*4 and CYP2D6*10 alleles in both chronically tramadol-treated and control groups.	Tramadol	145-153	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	82-88
29555325-3	2018	In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&amp;*10), suggesting oxidative stress.	Tramadol	3-11	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	30-36
29555325-3	2018	In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&amp;*10), suggesting oxidative stress.	Tramadol	3-11	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	84-90
29555325-3	2018	In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&amp;*10), suggesting oxidative stress.	Tramadol	3-11	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	84-90
29555325-3	2018	In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&amp;*10), suggesting oxidative stress.	Tramadol	129-137	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	30-36
29555325-3	2018	In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&amp;*10), suggesting oxidative stress.	Tramadol	129-137	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	84-90
29555325-3	2018	In tramadol-treated patients, CYP2D6*DUP allele carriers followed by those carrying CYP2D6*1, displayed higher levels of urinary tramadol major active metabolite, O-desmethyltramadol (M1) and serum lipid peroxidation along with lower levels of total antioxidants than those carrying other impaired function alleles (CYP2D6*4&amp;*10), suggesting oxidative stress.	Tramadol	129-137	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	84-90
29555325-6	2018	Overall, our results suggest that CYP2D6 gene polymorphisms, particularly enhanced or normal function of CYP2D6, may increase the vulnerability to long term tramadol-induced hepatotoxicity through the enhancement of accumulation of tramadol bioactive metabolite (M1) and hence oxidative stress.	Tramadol	157-165	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	34-40
29555325-6	2018	Overall, our results suggest that CYP2D6 gene polymorphisms, particularly enhanced or normal function of CYP2D6, may increase the vulnerability to long term tramadol-induced hepatotoxicity through the enhancement of accumulation of tramadol bioactive metabolite (M1) and hence oxidative stress.	Tramadol	157-165	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	105-111
29555325-6	2018	Overall, our results suggest that CYP2D6 gene polymorphisms, particularly enhanced or normal function of CYP2D6, may increase the vulnerability to long term tramadol-induced hepatotoxicity through the enhancement of accumulation of tramadol bioactive metabolite (M1) and hence oxidative stress.	Tramadol	232-240	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	34-40
29555325-6	2018	Overall, our results suggest that CYP2D6 gene polymorphisms, particularly enhanced or normal function of CYP2D6, may increase the vulnerability to long term tramadol-induced hepatotoxicity through the enhancement of accumulation of tramadol bioactive metabolite (M1) and hence oxidative stress.	Tramadol	232-240	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	105-111
29555325-7	2018	Therefore, tramadol doses should be adjusted according to patient"s CYP2D6 genotyping analysis to avoid hepatotoxicity.	Tramadol	11-19	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	68-74
29881433-0	2018	Gender Dependency in Streoselective Pharmacokinetics of Tramadol and Its Phase I Metabolites in Relation to CYP2D6 Phenotype in Iranian Population.	Tramadol	56-64	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	108-114
29881433-1	2018	The stereoselective pharmacokinetic of Tramadol (T) and its main metabolites concerning the influence of CYP2D6 phenotype and gender on the phase I metabolism of this compound was studied after administration of 100 mg single oral dose of racemic T to 24 male and female subjects.	Tramadol	39-47	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	105-111
29196917-1	2018	Tramadol is a centrally acting synthetic opioid analgesic and has received special attention due to its abuse potential and unexpected responses induced by CYP2D6 polymorphism.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	156-162
29556194-7	2018	Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity.	Tramadol	12-20	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	193-199
29556194-7	2018	Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity.	Tramadol	100-108	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	193-199
29556194-9	2018	To provide safe and effective tramadol prescription in children, a personalized approach, with dose adaptation according to CYP2D6 activity, would certainly be the safest method.	Tramadol	30-38	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	124-130
29196917-5	2018	Furthermore, the distribution of tramadol and its metabolites, in relation to CYP2D6 genetic variations, in oral fluid was investigated following a clinical study including 23 subjects with CYP2D6*wt/*wt, CYP2D6*10/*10 or CYP2D6*5/*5.	Tramadol	33-41	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	78-84
29196917-7	2018	Pharmacokinetic parameters, such as Css,max and AUC0-tau of tramadol, NDMT and NODMT, in the CYP2D6*10/*10 group were significantly higher than those in the CYP2D6*wt/*wt group.	Tramadol	60-68	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	93-99
29196917-8	2018	Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT correlated well with the CYP2D6 genotypes.	Tramadol	29-37	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	93-99
29714124-3	2018	Clinical recommendations exist to guide drug therapy based on CYP2D6 genotype for codeine, tramadol, oxycodone and hydrocodone, although the level of supporting evidence differs by drug.	Tramadol	91-99	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	62-68
29190510-2	2018	Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process.	Tramadol	187-195	UDP glucuronosyltransferase family 2 member B7	Homo sapiens	40-46
29190510-2	2018	Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process.	Tramadol	187-195	ATP binding cassette subfamily B member 1	Homo sapiens	48-53
29190510-2	2018	Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process.	Tramadol	187-195	opioid receptor mu 1	Homo sapiens	55-60
29190510-2	2018	Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process.	Tramadol	187-195	catechol-O-methyltransferase	Homo sapiens	66-70
29801577-5	2018	SNPs in the cytochrome P450 enzymes genes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone, and tricyclic antidepressants.	Tramadol	84-92	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	43-49
29210063-7	2018	KEY RESULTS: Dextromethorphan, l(R)-methadone, racemic methadone, pethidine, tramadol and tapentadol inhibited the SERT at or close to observed drug plasma or estimated brain concentrations in patients.	Tramadol	77-85	solute carrier family 6 member 4	Homo sapiens	115-119
29210063-14	2018	SERT inhibition by tramadol, tapentadol, methadone, dextromethorphan and pethidine may contribute to the serotonin syndrome.	Tramadol	19-27	solute carrier family 6 member 4	Homo sapiens	0-4
28772090-9	2018	Pre-test intra-CA1 injection of DL-AP5 (0.25 and 0.5 mug/mouse) reversed the memory impairment induced by post-training administration of tramadol (5 mg/kg).	Tramadol	138-146	carbonic anhydrase 1	Mus musculus	15-18
28772090-11	2018	It can be concluded that dorsal hippocampal NMDAR mechanisms play an important role in the modulation of tramadol state-dependent memory.	Tramadol	105-113	glutamate receptor, ionotropic, NMDA1 (zeta 1)	Mus musculus	44-49
29317054-3	2018	On the other hand, tramadol that is a very well tolerated opioid analgesic has been revealed to inhibit mTOR upstream controllers through interaction with specific types of muscarinic, serotonergic, nicotinic and NMDA receptors, although it seems to induce the opposite effect via micro-opioid receptor.	Tramadol	19-27	mechanistic target of rapamycin kinase	Homo sapiens	104-108
29115581-0	2018	Tramadol attenuates the sensitivity of glioblastoma to temozolomide through the suppression of Cx43-mediated gap junction intercellular communication.	Tramadol	0-8	gap junction protein alpha 1	Homo sapiens	95-99
29115581-8	2018	Tramadol treatment for 72 h did not alter Cx43 expression, but decreased Cx43 phosphorylation accompanied with reduced p-ERK and p-JNK.	Tramadol	0-8	gap junction protein alpha 1	Homo sapiens	73-77
29115581-9	2018	Our results indicated that long-term treatment with tramadol reduced TMZ cytotoxicity in U87 cells by suppressing Cx43-composed gap junctions, suggesting identification and usage of antinociceptive drugs which do not downregulate connexin activity should have beneficial therapeutic consequences.	Tramadol	52-60	gap junction protein alpha 1	Homo sapiens	114-118
29317054-4	2018	Putting all the pieces of experimental evidence together, we hypothesize that tramadol might alleviate AD pathological hallmarks at least in cellular level through decreasing activity of PI3K-AKT and ERK and also mTOR signaling pathways respectively and results in autophagy activation as well as tau-dephosphorylation.	Tramadol	78-86	AKT serine/threonine kinase 1	Homo sapiens	192-195
29317054-4	2018	Putting all the pieces of experimental evidence together, we hypothesize that tramadol might alleviate AD pathological hallmarks at least in cellular level through decreasing activity of PI3K-AKT and ERK and also mTOR signaling pathways respectively and results in autophagy activation as well as tau-dephosphorylation.	Tramadol	78-86	mitogen-activated protein kinase 1	Homo sapiens	200-203
29317054-4	2018	Putting all the pieces of experimental evidence together, we hypothesize that tramadol might alleviate AD pathological hallmarks at least in cellular level through decreasing activity of PI3K-AKT and ERK and also mTOR signaling pathways respectively and results in autophagy activation as well as tau-dephosphorylation.	Tramadol	78-86	mechanistic target of rapamycin kinase	Homo sapiens	213-217
29317054-4	2018	Putting all the pieces of experimental evidence together, we hypothesize that tramadol might alleviate AD pathological hallmarks at least in cellular level through decreasing activity of PI3K-AKT and ERK and also mTOR signaling pathways respectively and results in autophagy activation as well as tau-dephosphorylation.	Tramadol	78-86	microtubule associated protein tau	Homo sapiens	297-300
28699646-8	2017	The Clinical Pharmacogenetics Implementation Consortium guidelines provide CYP2D6-guided therapeutic recommendations to individualize treatment with tramadol and codeine.	Tramadol	149-157	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	75-81
28481389-18	2018	In the CCI-CCR-tramadol treatment group, TNF-?	Tramadol	15-23	tumor necrosis factor	Rattus norvegicus	41-44
29241501-7	2017	In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol.	Tramadol	99-107	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	41-47
29061087-6	2017	This review summarize the data on the effect of OCT1 polymorphisms on pharmacokinetics and efficacy of opioids like morphine, codeine, and tramadol and of anti-migraine drugs.	Tramadol	139-147	solute carrier family 22 member 1	Homo sapiens	48-52
29066180-9	2018	The mean tramadol plasma concentration after self-administration remained &gt;100 ng mL-1 throughout consumption time.	Tramadol	9-17	L1 cell adhesion molecule	Mus musculus	85-89
28591692-4	2017	NMDA-NR1 was measured in the cerebral tissue of rats with inflammation (complete Freund"s adjuvent) and those injected with tramadol after RFR exposure (RFR, RFR/TRAM) and in non-exposed (baseline, TRAM) rats.	Tramadol	124-132	glutamate ionotropic receptor NMDA type subunit 1	Rattus norvegicus	0-8
28769582-9	2017	CONCLUSION: Our results suggest that &gt;30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone.	Tramadol	166-174	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	83-89
27111538-9	2017	Tramadol"s ICER was highly sensitive to its effect on TKA outcomes.	Tramadol	0-8	cAMP responsive element modulator	Homo sapiens	11-15
28303368-5	2017	Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-gamma and IL-4.	Tramadol	9-17	interferon gamma	Homo sapiens	209-218
28303368-7	2017	We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol.	Tramadol	89-97	signal transducer and activator of transcription 6	Homo sapiens	19-24
28799579-2	2017	A tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed combination (TRAM/DKP 75 mg/25 mg) has been recently registered and released in Europe for the treatment of moderate-to-severe acute pain.	Tramadol	2-24	translocation associated membrane protein 1	Homo sapiens	75-79
28616923-0	2017	[Effects of Tramadol on Insulin Resistance during Cesarean Section Complicated with Gestational Diabetes Mellitus].	Tramadol	12-20	insulin	Homo sapiens	24-31
28616923-1	2017	OBJECTIVES: To investigate the effects of tramadol on insulin resistance (IR) during cesarean section complicated with gestational diabetes mellitus (GDM).	Tramadol	42-50	insulin	Homo sapiens	54-61
28616923-9	2017	CONCLUSIONS: The tramadol can attenuate IR during cesarean section complicated with GDM and may regulate the secretion of IL-6, TNF-alpha and PI3K/Akt signaling pathway in the treatment of IR of GDM.	Tramadol	17-25	interleukin 6	Homo sapiens	122-126
28616923-9	2017	CONCLUSIONS: The tramadol can attenuate IR during cesarean section complicated with GDM and may regulate the secretion of IL-6, TNF-alpha and PI3K/Akt signaling pathway in the treatment of IR of GDM.	Tramadol	17-25	tumor necrosis factor	Homo sapiens	128-137
27958259-1	2017	Acute hyperkinesia after discontinuation of tramadol in a patient with chronic pain using citalopram and pramipexole for restless legs syndrome (RLS) has not been reported.	Tramadol	44-52	RLS1	Homo sapiens	145-148
27861439-3	2017	The opioid analgesic potency of a given dose of tramadol is influenced by an individual"s CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects.	Tramadol	48-56	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	90-93
27861439-4	2017	The importance of the CYP metabolism has led to the adoption of computer clinical decision support with pharmacogenomics tools guiding tramadol treatment in major medical centers.	Tramadol	135-143	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	22-25
27861439-7	2017	This review provides updated important information on the pharmacology, pharmacokinetics, CYP genetic polymorphisms, drug interactions, toxicity, withdrawal, and illicit use of tramadol.	Tramadol	177-185	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	90-93
27958259-6	2017	Obviously, tramadol withdrawal had enhanced the preexisting RLS.	Tramadol	11-19	RLS1	Homo sapiens	60-63
27958259-8	2017	Sudden discontinuation of tramadol in a patient under pramipexole for RLS may cause severe, choreatic hyperkinesias for hours, which immediately resolve upon intravenous fentanyl.	Tramadol	26-34	RLS1	Homo sapiens	70-73
27958259-9	2017	In patients under pramipexole for RLS and tramadol and fentanyl for chronic pain, sudden discontinuation of tramadol should be avoided to prevent induction of restless body syndrome.	Tramadol	108-116	RLS1	Homo sapiens	34-37
27580162-3	2016	Tramadol is mainly metabolized by cytochrome P450 CYP2D6 to O-desmethyltramadol (M1), its main active metabolite.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	50-56
28768953-0	2017	Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.	Tramadol	11-19	coagulation factor II, thrombin	Homo sapiens	40-51
25370921-0	2016	Interaction of a Cannabinoid-2 Agonist With Tramadol on Nociceptive Thresholds and Immune Responses in a Rat Model of Incisional Pain.	Tramadol	44-52	cannabinoid receptor 2	Rattus norvegicus	17-30
25370921-1	2016	The aim of this study was to elucidate the antinociceptive interaction between cannabinoids and tramadol and their impact on proinflammatory response, in terms of serum intereleukin-6 (IL-6) and interleukin-2 (IL-2) release, in a rat model of incisional pain.	Tramadol	96-104	interleukin 2	Rattus norvegicus	210-214
25370921-13	2016	It seems that the concomitant administration of a selective CB-2 agonist with tramadol in incisional pain model may improve antinociceptive effects and immune responses of cannabinoids, but this effect does not seem to be superior to that of tramadol alone.	Tramadol	78-86	cannabinoid receptor 2	Rattus norvegicus	60-64
27890370-0	2016	Acetylcholinesterase, butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis, tramadol or both.	Tramadol	104-112	acetylcholinesterase	Rattus norvegicus	0-20
27890370-0	2016	Acetylcholinesterase, butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis, tramadol or both.	Tramadol	104-112	paraoxonase 1	Rattus norvegicus	48-61
27890370-1	2016	OBJECTIVE: To investigate the effect of Cannabis sativa resin and/or tramadol, two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.	Tramadol	69-77	acetylcholinesterase	Rattus norvegicus	110-130
27890370-1	2016	OBJECTIVE: To investigate the effect of Cannabis sativa resin and/or tramadol, two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.	Tramadol	69-77	butyrylcholinesterase	Rattus norvegicus	135-156
27890370-9	2016	In contrast, tramadol given at 5, 10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%, 36.7%, and 46.1%, respectively.	Tramadol	13-21	paraoxonase 1	Rattus norvegicus	97-101
27890370-10	2016	Meanwhile, treatment with cannabis resin plus tramadol resulted in 40.2%, 35.8%, 30.7% inhibition of PON1 activity compared to the saline group.	Tramadol	46-54	paraoxonase 1	Rattus norvegicus	101-105
27388970-4	2016	CYP2D6 polymorphism is well known for its variation in the metabolism of drugs from many therapeutic arenas, including some analgesic drugs such as codeine, hydromorphone, oxycodone and tramadol.	Tramadol	186-194	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
27541716-0	2016	Loss-of-function polymorphisms in the organic cation transporter OCT1 are associated with reduced postoperative tramadol consumption.	Tramadol	112-120	solute carrier family 22 member 1	Homo sapiens	65-69
27541716-1	2016	The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+)O-desmethyltramadol in the liver.	Tramadol	91-99	solute carrier family 22 member 1	Homo sapiens	31-35
27541716-1	2016	The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+)O-desmethyltramadol in the liver.	Tramadol	91-99	solute carrier family 22 member 1	Homo sapiens	37-44
27541716-2	2016	In this study, the influence of OCT1 genetic polymorphisms on pharmacokinetics and analgesic efficacy of tramadol in patients recovering from surgery was analyzed in addition to the CYP2D6 genotype.	Tramadol	105-113	solute carrier family 22 member 1	Homo sapiens	32-36
27541716-5	2016	The primary endpoint was the 24-hour postoperative tramadol consumption in patients with 0 vs at least 1 active OCT1 allele.	Tramadol	51-59	solute carrier family 22 member 1	Homo sapiens	112-116
27541716-6	2016	Secondary endpoint was the OCT1-dependent plasma concentration (areas under the concentration-time curves) of the active tramadol metabolite (+)O-desmethyltramadol.	Tramadol	121-129	solute carrier family 22 member 1	Homo sapiens	27-31
27541716-8	2016	Cumulative tramadol consumption through patient-controlled analgesia was lowest in patients with 0 active OCT1 allele compared with the group of patients with 1 or 2 active alleles (343 +- 235 vs 484 +- 276 mg; P = 0.03).	Tramadol	11-19	solute carrier family 22 member 1	Homo sapiens	106-110
27541716-11	2016	Loss of OCT1 function resulted in reduced tramadol consumption and increased plasma concentrations of (+)O-desmethyltramadol in patients recovering from surgery.	Tramadol	42-50	solute carrier family 22 member 1	Homo sapiens	8-12
27541716-12	2016	Therefore, analyzing OCT1 next to CYP2D6 genotype might further improve future genotype-dependent dose recommendations for tramadol.	Tramadol	123-131	solute carrier family 22 member 1	Homo sapiens	21-25
27089282-3	2016	Post-training intra-CA1 administration of an atypical mu-opioid receptor agonist, tramadol (0.5 and 1 mug/mouse), dose dependently impaired memory retention.	Tramadol	82-90	carbonic anhydrase 1	Mus musculus	20-23
27552701-8	2016	The highest mean specific load of tramadol was detected in the spa town of Piestany (371mg/day/1000 inhabitants) and Kosice (372mg/day/1000 inhabitants), while the highest mean loads of venlafaxine were recorded for the towns of Trencin (230mg/day/1000 inhabitants) and Piestany (108mg/day/1000 inhabitants).	Tramadol	34-42	surfactant protein A2	Homo sapiens	63-66
27138295-5	2016	Multiple factors may have contributed to these observations, including a higher proportion of children (56%) who may have a lower activity of CYP2D6, resulting in reduced clearance of tramadol.	Tramadol	184-192	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	142-148
27531573-3	2016	Conversely, tramadol hydrochloride/acetaminophen combination (TRAM/APAP) therapy has been shown to reduce pain, particularly for chronic pain in Japan.	Tramadol	12-34	translocation associated membrane protein 1	Homo sapiens	62-66
27470363-11	2016	We recorded a significant increase MDA level, while antioxidant enzymes; GSH, SOD and CAT were significantly decreased after tramadol-treatment.	Tramadol	125-133	catalase	Rattus norvegicus	86-89
27470363-13	2016	On molecular level, the expression of the pro-apoptotic Bax and Caspase-3 showed a significant increase whereas the anti-apoptotic Bcl-2 decreased markedly indicating that tramadol is harmful at cellular level and can induce apoptotic changes in brain tissues.	Tramadol	172-180	BCL2 associated X, apoptosis regulator	Rattus norvegicus	56-59
27470363-13	2016	On molecular level, the expression of the pro-apoptotic Bax and Caspase-3 showed a significant increase whereas the anti-apoptotic Bcl-2 decreased markedly indicating that tramadol is harmful at cellular level and can induce apoptotic changes in brain tissues.	Tramadol	172-180	caspase 3	Rattus norvegicus	64-73
27470363-13	2016	On molecular level, the expression of the pro-apoptotic Bax and Caspase-3 showed a significant increase whereas the anti-apoptotic Bcl-2 decreased markedly indicating that tramadol is harmful at cellular level and can induce apoptotic changes in brain tissues.	Tramadol	172-180	BCL2, apoptosis regulator	Rattus norvegicus	131-136
26867125-6	2016	Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1beta induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1beta.	Tramadol	32-40	interleukin 1 beta	Mus musculus	101-109
26867125-6	2016	Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1beta induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1beta.	Tramadol	32-40	interleukin 1 beta	Mus musculus	247-255
26867125-8	2016	Gabapentin or tramadol or their combination modulates the expression of pro-inflammatory cytokine, IL-1beta, in a model of mice PSNL which could be due to an inhibition of glial function.	Tramadol	14-22	interleukin 1 beta	Mus musculus	99-107
27089282-4	2016	Pretest injection of tramadol (0.5 and 1 mug/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under the influence of post-training tramadol (1 mug/mouse, intra-CA1).	Tramadol	21-29	carbonic anhydrase 1	Mus musculus	58-61
27089282-4	2016	Pretest injection of tramadol (0.5 and 1 mug/mouse, intra-CA1) induced state-dependent retrieval of the memory acquired under the influence of post-training tramadol (1 mug/mouse, intra-CA1).	Tramadol	21-29	carbonic anhydrase 1	Mus musculus	186-189
27089282-5	2016	A pretest intra-CA1 injection of physostigmine (1 mug/mouse) reversed the memory impairment induced by post-training administration of tramadol (1 mug/mouse, intra-CA1).	Tramadol	135-143	carbonic anhydrase 1	Mus musculus	16-19
27089282-5	2016	A pretest intra-CA1 injection of physostigmine (1 mug/mouse) reversed the memory impairment induced by post-training administration of tramadol (1 mug/mouse, intra-CA1).	Tramadol	135-143	carbonic anhydrase 1	Mus musculus	164-167
27089282-8	2016	A pretest intra-CA1 injection of the atropine (1 and 2 mug/mouse) 5 min before the administration of tramadol (1 mug/mouse, intra-CA1) dose dependently inhibited tramadol state-dependent memory.	Tramadol	101-109	carbonic anhydrase 1	Mus musculus	130-133
27089282-8	2016	A pretest intra-CA1 injection of the atropine (1 and 2 mug/mouse) 5 min before the administration of tramadol (1 mug/mouse, intra-CA1) dose dependently inhibited tramadol state-dependent memory.	Tramadol	162-170	carbonic anhydrase 1	Mus musculus	16-19
27089282-8	2016	A pretest intra-CA1 injection of the atropine (1 and 2 mug/mouse) 5 min before the administration of tramadol (1 mug/mouse, intra-CA1) dose dependently inhibited tramadol state-dependent memory.	Tramadol	162-170	carbonic anhydrase 1	Mus musculus	130-133
23567787-0	2016	CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.	Tramadol	58-66	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
27463799-9	2016	Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001).	Tramadol	80-88	myeloperoxidase	Rattus norvegicus	8-23
27383307-9	2016	The data also revealed that tramadol could up-regulate the protein expression level of PTEN and consistently inhibit the phosphorylation level of PI3K and Akt, whereas the total level of PI3K and Akt remain unchanged.	Tramadol	28-36	phosphatase and tensin homolog	Homo sapiens	87-91
27383307-9	2016	The data also revealed that tramadol could up-regulate the protein expression level of PTEN and consistently inhibit the phosphorylation level of PI3K and Akt, whereas the total level of PI3K and Akt remain unchanged.	Tramadol	28-36	AKT serine/threonine kinase 1	Homo sapiens	155-158
27383307-10	2016	CONCLUSIONS: These findings indicated that tramadol inhibited proliferation, migration and invasion of human lung adenocarcinoma cells through elevation of PTEN and inactivation of PI3K/Akt signaling.	Tramadol	43-51	phosphatase and tensin homolog	Homo sapiens	156-160
27383307-10	2016	CONCLUSIONS: These findings indicated that tramadol inhibited proliferation, migration and invasion of human lung adenocarcinoma cells through elevation of PTEN and inactivation of PI3K/Akt signaling.	Tramadol	43-51	AKT serine/threonine kinase 1	Homo sapiens	186-189
26441153-6	2016	Prior to drug administration, the ability of recombinant CYP2D50 to metabolize tramadol to O-desmethyltramadol was confirmed.	Tramadol	79-87	cytochrome P450 family 2 subfamily D member 50	Equus caballus	57-64
26926096-0	2016	Sequencing CYP2D6 for the detection of poor-metabolizers in post-mortem blood samples with tramadol.	Tramadol	91-99	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	11-17
26926096-1	2016	Tramadol concentrations and analgesic effect are dependent on the CYP2D6 enzymatic activity.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	66-72
27082504-1	2016	BACKGROUND: This study determined whether the SLC22A1 [encoding the organic cation transporter 1 (OCT1)] genotype could explain, in addition to the postmenstrual age (referring to gestational plus postnatal age) and CYP2D6 genotype, the tramadol (M) pharmacokinetic variability in early infancy.	Tramadol	237-245	solute carrier family 22 member 1	Homo sapiens	46-53
27082504-1	2016	BACKGROUND: This study determined whether the SLC22A1 [encoding the organic cation transporter 1 (OCT1)] genotype could explain, in addition to the postmenstrual age (referring to gestational plus postnatal age) and CYP2D6 genotype, the tramadol (M) pharmacokinetic variability in early infancy.	Tramadol	237-245	solute carrier family 22 member 1	Homo sapiens	68-96
27082504-1	2016	BACKGROUND: This study determined whether the SLC22A1 [encoding the organic cation transporter 1 (OCT1)] genotype could explain, in addition to the postmenstrual age (referring to gestational plus postnatal age) and CYP2D6 genotype, the tramadol (M) pharmacokinetic variability in early infancy.	Tramadol	237-245	solute carrier family 22 member 1	Homo sapiens	98-102
27383307-0	2016	Tramadol regulates proliferation, migration and invasion via PTEN/PI3K/AKT signaling in lung adenocarcinoma cells.	Tramadol	0-8	phosphatase and tensin homolog	Homo sapiens	61-65
27383307-0	2016	Tramadol regulates proliferation, migration and invasion via PTEN/PI3K/AKT signaling in lung adenocarcinoma cells.	Tramadol	0-8	AKT serine/threonine kinase 1	Homo sapiens	71-74
23567787-3	2016	The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol.	Tramadol	294-302	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	52-58
26813469-8	2016	Furthermore, the protein levels of alpha2-adrenoceptor and phosphorylated ERK were decreased by tramadol, whereas the expression of total ERK remained unchanged.	Tramadol	96-104	mitogen-activated protein kinase 1	Homo sapiens	74-77
26947771-0	2016	Impact of fraction unbound, CYP3A, and CYP2D6 in vivo activities, and other potential covariates to the clearance of tramadol enantiomers in patients with neuropathic pain.	Tramadol	117-125	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	39-45
26947771-1	2016	The pharmacokinetics of tramadol is characterized by a large interindividual variability, which is partially attributed to polymorphic CYP2D6 metabolism.	Tramadol	24-32	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	135-141
26947771-7	2016	Between 79 and 83% of the overall variation in apparent clearance of tramadol enantiomers was explained by fraction unbound, CYP2D6, and CYP3A in vivo activities and body weight.	Tramadol	69-77	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	125-131
26947771-7	2016	Between 79 and 83% of the overall variation in apparent clearance of tramadol enantiomers was explained by fraction unbound, CYP2D6, and CYP3A in vivo activities and body weight.	Tramadol	69-77	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	137-142
26947771-9	2016	Individually, CYP2D6 and CYP3A activities were shown to have moderate contribution on clearance of tramadol enantiomers (11-16% and 11-18%, respectively).	Tramadol	99-107	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
26947771-9	2016	Individually, CYP2D6 and CYP3A activities were shown to have moderate contribution on clearance of tramadol enantiomers (11-16% and 11-18%, respectively).	Tramadol	99-107	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	25-30
26979111-9	2016	Drivers consuming Tramadol (adjusted OR 11.41; 95% CI 1.27, 102.15) were at a significantly increased risk of motor vehicle collision.	Tramadol	18-26	olfactory receptor family 4 subfamily F member 16	Homo sapiens	37-42
26706288-7	2016	Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release.	Tramadol	41-49	calcitonin-related polypeptide alpha	Rattus norvegicus	131-135
27042732-5	2016	The potency of codeine and tramadol is strongly influenced by the cytochrome P450 isoenzyme CYP2D6 genotype, which varies widely from one person to another.	Tramadol	27-35	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	92-98
26313333-2	2015	Here, a solid-phase microextraction (SPME) coating that combines octadecyl and propylsulfonic acid groups as strong cation exchange sites, known as C18/SCX or "mixed-mode" SPME, is used to measure freely dissolved concentrations of amitriptyline, amphetamine, diazepam and tramadol to different binding matrices, including bovine serum albumin (BSA), human serum albumin (HSA), human plasma and human whole blood.	Tramadol	273-281	Bardet-Biedl syndrome 9	Homo sapiens	148-151
26508138-6	2015	RESULTS: NCA demonstrated comparable maximum plasma concentration (C max) and AUC between age groups for tramadol enantiomers, but significant differences in V area/ F (mean 34% higher) and k el (mean 28% lower) in the elderly.	Tramadol	105-113	CEA cell adhesion molecule 6	Homo sapiens	9-12
26544960-10	2015	Overall the results show that VCPKMT is an enzyme required for methylation of K315 of VCP in vivo, but VCPKMT is not essential for development or survival under unstressed conditions.	Tramadol	78-82	valosin containing protein lysine (K) methyltransferase	Mus musculus	30-36
26209290-2	2015	An intravenous tramadol retrograde PBPK model was set up in Simcyp  using adult clearance values, qualified for CYP2D6, CYP3A4, CYP2B6, and renal contributions.	Tramadol	15-23	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	112-118
26544960-10	2015	Overall the results show that VCPKMT is an enzyme required for methylation of K315 of VCP in vivo, but VCPKMT is not essential for development or survival under unstressed conditions.	Tramadol	78-82	valosin containing protein	Mus musculus	30-33
26297302-6	2015	The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-alpha).	Tramadol	46-54	transient receptor potential cation channel, subfamily V, member 1	Mus musculus	163-168
26297302-6	2015	The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-alpha).	Tramadol	46-54	peroxisome proliferator activated receptor alpha	Mus musculus	175-223
26297302-6	2015	The antinociceptive mechanisms of the PEA and tramadol combination involved the opioid receptor, transient receptor potential cation channel subfamily V member 1 (TRPV1), and peroxisome proliferator-activated receptor alpha (PPAR-alpha).	Tramadol	46-54	peroxisome proliferator activated receptor alpha	Mus musculus	225-235
26678969-6	2015	Although it has not been studied in patients with cancer-related pain, the effect of CYP2D6 variation is well characterized with codeine and tramadol.	Tramadol	141-149	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	85-91
26031356-0	2015	Sex hormones regulate cerebral drug metabolism via brain miRNAs: down-regulation of brain CYP2D by androgens reduces the analgesic effects of tramadol.	Tramadol	142-150	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	90-95
26031356-10	2015	Changes in the pharmacokinetic and pharmacodynamic profiles of tramadol by orchiectomy was attenuated by either testosterone supplementation or a specific brain CYP2D inhibitor.	Tramadol	63-71	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	161-166
26447442-3	2015	For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel.	Tramadol	158-166	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	40-59
26447442-4	2015	If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness.	Tramadol	123-131	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	77-83
25719307-7	2015	The O-demethylation of codeine and tramadol to their respective my-opioid active metabolites, morphine and (+)-O-desmethyltramadol was markedly impaired in CYP2D6 poor metabolizers compared to extensive metabolizers, and this impairs the hypoalgesic effect of the two drugs in the poor metabolizers.	Tramadol	35-43	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	156-162
28520365-0	2012	Tramadol Therapy and CYP2D6 Genotype Tramadol is an analgesic used to treat moderate to moderately severe pain.	Tramadol	37-45	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	21-27
28520365-3	2012	The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, including tramadol.	Tramadol	75-83	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	4-10
28520365-4	2012	Individuals who carry two inactive copies of CYP2D6 are known as poor metabolizers and have higher plasma concentrations of tramadol compared with individuals who have two copies of normal activity alleles (1).	Tramadol	124-132	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	45-51
28520365-7	2012	Inhibitors of CYP2D6, such as fluoxetine and amitriptyline, also inhibit the metabolism of tramadol, and the full pharmacological impact of these alterations of tramadol dose in terms of either efficacy or safety is unknown (1).	Tramadol	91-99	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
28520365-7	2012	Inhibitors of CYP2D6, such as fluoxetine and amitriptyline, also inhibit the metabolism of tramadol, and the full pharmacological impact of these alterations of tramadol dose in terms of either efficacy or safety is unknown (1).	Tramadol	161-169	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
25910878-4	2015	METHOD: A systematic literature search was conducted in PubMed and EMBASE involving all metabolic enzymes, drug transporters and receptors, as well as SERT and NET that are involved in the pharmacokinetics and pharmacodynamics of tramadol.	Tramadol	230-238	solute carrier family 6 member 4	Homo sapiens	151-155
26367475-0	2015	Differential Consequences of Tramadol in Overdosing: Dilemma of a Polymorphic Cytochrome P450 2D6-Mediated Substrate.	Tramadol	29-37	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	78-97
26367475-1	2015	Tramadol is a centrally acting opioid analgesic that is prone to polymorphic metabolism via cytochrome P450 (CYP) 2D6.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	92-117
26367475-5	2015	Depending on the individual subject"s CYP 2D6 status, one may see excessive miotic-related toxicity driven by the excessive availability of O-desmethyltramadol or one may manifest mydriatic-related toxicity driven by the excessive availability of tramadol.	Tramadol	151-159	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	38-45
25910878-8	2015	Only the effect of CYP2D6 polymorphisms on the metabolism of tramadol and the consequent effect on pain relief has been thoroughly studied and sufficiently established as clinically relevant.	Tramadol	61-69	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	19-25
25948472-0	2015	Effect of the CYP2D6 gene polymorphism on postoperative analgesia of tramadol in Han nationality nephrectomy patients.	Tramadol	69-77	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
25998998-11	2015	CYP2D6 ultra-rapid metabolisers are more likely to experience the adverse effects of codeine and tramadol.	Tramadol	97-105	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
25948472-3	2015	Patients with different CYP2D6 genotypes would have different responses to tramadol in pain relief.	Tramadol	75-83	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	24-30
25948472-5	2015	The aim of this study was to evaluate whether the different CYP2D6*10 genotypes have an effect on the postoperative tramadol analgesia in the Chinese population after elective nephrectomy.	Tramadol	116-124	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
25948472-18	2015	CONCLUSIONS: Different CYP2D6*10 genotypes have an influence on the analgesic effect of tramadol in Han nationality patients after elective nephrectomy.	Tramadol	88-96	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	23-29
25387586-0	2015	Regulation of cerebral CYP2D alters tramadol metabolism in the brain: interactions of tramadol with propranolol and nicotine.	Tramadol	36-44	cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)	Homo sapiens	23-28
25642661-0	2015	Tramadol and its metabolite m1 selectively suppress transient receptor potential ankyrin 1 activity, but not transient receptor potential vanilloid 1 activity.	Tramadol	0-8	transient receptor potential cation channel subfamily A member 1	Homo sapiens	52-90
25642661-6	2015	TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively.	Tramadol	34-42	transient receptor potential cation channel subfamily V member 1	Homo sapiens	0-5
25642661-6	2015	TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively.	Tramadol	34-42	transient receptor potential cation channel subfamily A member 1	Homo sapiens	10-15
25642661-7	2015	METHODS: We examined whether and how tramadol and M1 act on human embryonic kidney 293 (HEK293) cells expressing human TRPV1 (hTRPV1) or hTRPA1 by using a Ca imaging assay and whole-cell patch-clamp recording.	Tramadol	37-45	transient receptor potential cation channel subfamily V member 1	Homo sapiens	119-124
25642661-7	2015	METHODS: We examined whether and how tramadol and M1 act on human embryonic kidney 293 (HEK293) cells expressing human TRPV1 (hTRPV1) or hTRPA1 by using a Ca imaging assay and whole-cell patch-clamp recording.	Tramadol	37-45	transient receptor potential cation channel subfamily V member 1	Homo sapiens	126-132
25642661-10	2015	Conversely, pretreatment with tramadol (0.1-10 muM) and M1 (1-10 muM) significantly suppressed the AITC-induced [Ca]i increases in HEK293 cells expressing hTRPA1.	Tramadol	30-38	latexin	Homo sapiens	47-50
25642661-10	2015	Conversely, pretreatment with tramadol (0.1-10 muM) and M1 (1-10 muM) significantly suppressed the AITC-induced [Ca]i increases in HEK293 cells expressing hTRPA1.	Tramadol	30-38	transient receptor potential cation channel subfamily A member 1	Homo sapiens	155-161
25642661-11	2015	In addition, the patch-clamp study showed that pretreatment with tramadol and M1 (10 muM) decreased the inward currents induced by AITC.	Tramadol	65-73	latexin	Homo sapiens	85-88
25642661-12	2015	CONCLUSIONS: These data indicate that tramadol and M1 selectively inhibit the function of hTRPA1, but not that of hTRPV1, and that hTRPA1 may play a role in the analgesic effects of these compounds.	Tramadol	38-46	transient receptor potential cation channel subfamily A member 1	Homo sapiens	90-96
26028838-0	2015	A prospective study to assess the levels of interleukin-6 following administration of diclofenac, ketorolac and tramadol after surgical removal of lower third molars.	Tramadol	112-120	interleukin 6	Homo sapiens	44-57
26028838-7	2015	AIM: To evaluate the changes in serum IL-6 levels following surgical removal of third molars under local anaesthesia after administration of two NSAIDs diclofenac and ketorolac and opioid tramadol post operatively.	Tramadol	188-196	interleukin 6	Homo sapiens	38-42
26028838-11	2015	RESULTS: The results of our study showed that all three drugs i.e. diclofenac, ketorolac and tramadol have properties which can downregulate the production of IL-6 in response to surgical trauma.	Tramadol	93-101	interleukin 6	Homo sapiens	159-163
26028838-12	2015	CONCLUSION: It is of clinical significance that the suppression of IL-6 values occurs in tramadol group closely following the diclofenac group.	Tramadol	89-97	interleukin 6	Homo sapiens	67-71
26028838-13	2015	Even though the drug ketorolac suppresses the IL-6 levels similar to diclofenac initially but after 7 days tramadol and ketorolac showed similarities in suppression of IL-6 expression which is less compared to diclofenac group.	Tramadol	107-115	interleukin 6	Homo sapiens	168-172
25387586-0	2015	Regulation of cerebral CYP2D alters tramadol metabolism in the brain: interactions of tramadol with propranolol and nicotine.	Tramadol	86-94	cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)	Homo sapiens	23-28
25387586-11	2015	The results suggest that the regulation of brain CYP2D by xenobiotics may cause drug-drug interactions (DDIs) of tramadol.	Tramadol	113-121	cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)	Homo sapiens	49-54
25647677-0	2015	A case of respiratory depression in a child with ultrarapid CYP2D6 metabolism after tramadol.	Tramadol	84-92	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	60-66
25560051-3	2015	Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6.	Tramadol	0-8	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	100-106
25560051-3	2015	Tramadol is metabolized to M1 mainly by cytochrome P450 (CYP)2D6 enzyme and to other metabolites by CYP3A4 and CYP2B6.	Tramadol	0-8	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	111-117
25560051-4	2015	We investigated the possible interaction of tramadol with the antifungal agents terbinafine (CYP2D6 inhibitor) and itraconazole (CYP3A4 inhibitor).	Tramadol	44-52	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	93-99
25258277-1	2015	BACKGROUND AND OBJECTIVES: We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition.	Tramadol	162-170	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	80-99
26819716-1	2015	BACKGROUND: Tramadol ((+-)-TRA) is recommended for the treatment of mild to moderate cancer pain by the World Health Organization.	Tramadol	12-20	T cell receptor alpha locus	Homo sapiens	27-30
25258277-1	2015	BACKGROUND AND OBJECTIVES: We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition.	Tramadol	162-170	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	101-107
25222611-4	2014	In the presence of substrate tramadol, the electrochemical-driven CYP2D6 mediated catalytic behavior toward the conversion of tramadol to o-demethyl-tramadol was confirmed.	Tramadol	126-134	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	66-72
24975450-2	2015	Yet, it remains to be determined whether drug-drug interactions can affect this negative effect, for instance with drugs inhibiting cytochrome P4502D6 (CYP2D6) that metabolizes codeine and also has a partial effect on tramadol and oxycodone.	Tramadol	218-226	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	152-158
24975450-3	2015	Our aim was to investigate how CYP2D6-inhibiting drugs contribute to explaining the risk of fall-related injuries for newly initiated opioid treatments with codeine, tramadol or oxycodone.	Tramadol	166-174	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	31-37
24975450-8	2015	For tramadol, the risks were doubled when CYP2D6-inhibiting drugs were used (OR, 2.19; 95% CI 1.84-2.60) and tripled without their use (OR, 3.04; 95% CI 2.82-3.27).	Tramadol	4-12	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	42-48
24975450-10	2015	In newly initiated opioid therapies, drug-drug interactions from concomitant use of CYP2D6-inhibiting drugs are associated with a lower risk of fall-related injury for codeine and tramadol that undergo metabolism via CYP2D6, but not for other opioids.	Tramadol	180-188	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	84-90
24975450-10	2015	In newly initiated opioid therapies, drug-drug interactions from concomitant use of CYP2D6-inhibiting drugs are associated with a lower risk of fall-related injury for codeine and tramadol that undergo metabolism via CYP2D6, but not for other opioids.	Tramadol	180-188	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	217-223
25332055-7	2015	Tramadol, pethidine, and ketamine suppressed [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 muM, respectively.	Tramadol	0-8	latexin	Homo sapiens	113-116
25332055-9	2015	Free 5-HT concentrations in human plasma were increased by citalopram 1 muM, tramadol 20 muM, pethidine 30 muM, and ketamine 100 muM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p &lt; 0.005).	Tramadol	77-85	latexin	Homo sapiens	89-92
25332055-9	2015	Free 5-HT concentrations in human plasma were increased by citalopram 1 muM, tramadol 20 muM, pethidine 30 muM, and ketamine 100 muM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p &lt; 0.005).	Tramadol	77-85	latexin	Homo sapiens	89-92
25332055-9	2015	Free 5-HT concentrations in human plasma were increased by citalopram 1 muM, tramadol 20 muM, pethidine 30 muM, and ketamine 100 muM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95 % CI]; all p &lt; 0.005).	Tramadol	77-85	latexin	Homo sapiens	89-92
25332055-11	2015	Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets.	Tramadol	0-8	solute carrier family 6 member 4	Homo sapiens	37-53
25584932-4	2015	Black and Hispanic populations are known to have a higher prevalence of cardiovascular risk factors and disease, and a substantial proportion of black and Hispanic individuals possess genotypes of the cytochrome P450 (CYP) 2C9 enzyme involved in the metabolism of many NSAIDs and the CYP2D6 enzyme involved in metabolism of the dual opioid agonist/norepinephrine-serotonin reuptake inhibitor tramadol.	Tramadol	392-400	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	201-226
25584932-4	2015	Black and Hispanic populations are known to have a higher prevalence of cardiovascular risk factors and disease, and a substantial proportion of black and Hispanic individuals possess genotypes of the cytochrome P450 (CYP) 2C9 enzyme involved in the metabolism of many NSAIDs and the CYP2D6 enzyme involved in metabolism of the dual opioid agonist/norepinephrine-serotonin reuptake inhibitor tramadol.	Tramadol	392-400	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	284-290
26123824-9	2015	The highest percentage of responders (72%) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95% confidence interval 1.3 to 2.1).	Tramadol	99-121	cardiotrophin like cytokine factor 1	Homo sapiens	135-140
25222611-0	2014	Nanocomposites of graphene and cytochrome P450 2D6 isozyme for electrochemical-driven tramadol metabolism.	Tramadol	86-94	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	31-50
25222611-4	2014	In the presence of substrate tramadol, the electrochemical-driven CYP2D6 mediated catalytic behavior toward the conversion of tramadol to o-demethyl-tramadol was confirmed.	Tramadol	29-37	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	66-72
24492463-8	2014	Repeated administration of tramadol increased the dopamine beta-hydroxylase immunoreactivity in the spinal cord.	Tramadol	27-35	dopamine beta-hydroxylase	Rattus norvegicus	50-75
24717054-0	2014	Effects of type 1 and type 2 diabetes on the pharmacokinetics of tramadol enantiomers in patients with neuropathic pain phenotyped as cytochrome P450 2D6 extensive metabolizers.	Tramadol	65-73	cytochrome P450 2D6	Homo sapiens	134-153
24968714-0	2014	Using tramadol to measure CYP2D6 metabolism in critically ill adults.	Tramadol	6-14	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	26-32
25017386-6	2014	The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.	Tramadol	31-39	opioid receptor, mu 1	Mus musculus	93-96
25017386-6	2014	The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.	Tramadol	31-39	opioid receptor, delta 1	Mus musculus	98-101
25017386-6	2014	The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes.	Tramadol	31-39	opioid receptor, kappa 1	Mus musculus	106-109
24640604-0	2014	Effect of the cytochrome P450 2D6*10 genotype on the pharmacokinetics of tramadol in post-operative patients.	Tramadol	73-81	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-33
24640604-2	2014	Tramadol, a narcotic-like pain reliever used to treat moderate to severe pain, is primarily metabolized by CYP2D6.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	107-113
24640604-4	2014	Therefore, we investigated the effects of CYP2D6*10 on tramadol pharmacokinetics in 45 post-operative patients who had undergone gastrointestinal tract surgery.	Tramadol	55-63	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	42-48
24640604-13	2014	These results show that the CYP2D6*10 genetic polymorphism has a significant impact on the pharmacokinetics of tramadol in Chinese post-operative patients.	Tramadol	111-119	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	28-34
23759977-3	2014	This paper reviews the evidence on how CYP2D6 polymorphisms might influence pain sensitivity and clinical response to codeine and tramadol.	Tramadol	130-138	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	39-45
23759977-6	2014	Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia.	Tramadol	30-38	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	64-70
23759977-8	2014	The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol.	Tramadol	210-218	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	74-80
25014367-4	2014	Although polymorphic CYP2D6 appears to be a major enzyme involved in the metabolism of tramadol, application of a mixture model to test the assumption of two and three subpopulations did not reveal any improvement of the model.	Tramadol	87-95	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	21-27
24950410-0	2014	Higher frequency of C.3435 of the ABCB1 gene in patients with tramadol dependence disorder.	Tramadol	62-70	ATP binding cassette subfamily B member 1	Homo sapiens	34-39
24950410-2	2014	AIM: This study aimed to determine the frequency of occurrence of Single Nucleotide Polymorphism (SNP) in position A118G OPRM1 (rs1799971) gene and C.3435 (rs1045642) gene in tramadol users in comparison with normal controls.	Tramadol	175-183	opioid receptor mu 1	Homo sapiens	121-126
24950410-7	2014	RESULTS: A significant association was found between the ABCB1 gene T allele at the polymorphic site 3435 and tramadol dependence.	Tramadol	110-118	ATP binding cassette subfamily B member 1	Homo sapiens	57-62
24950410-9	2014	CONCLUSION: The high frequency of ABCB1 gene T allele present at the polymorphic site 3435 could provide a protective mechanism from tramadol dependence disorder.	Tramadol	133-141	ATP binding cassette subfamily B member 1	Homo sapiens	34-39
24423243-0	2014	Occupancy of serotonin transporter by tramadol: a positron emission tomography study with [11C]DASB.	Tramadol	38-46	solute carrier family 6 member 4	Homo sapiens	13-34
24423243-3	2014	However, there has been no report of 5-HT transporter (5-HTT) occupancy by tramadol at clinical doses in humans.	Tramadol	75-83	solute carrier family 6 member 4	Homo sapiens	37-53
24624916-1	2014	AIM: This study was performed to develop an algorithm using polymorphisms of CYP2D6, p-gp, OPRM1, COMT and psychological variables to predict tramadol response in Chinese patients recovering from upper limb fracture internal fixation surgery.	Tramadol	142-150	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	77-83
24624916-1	2014	AIM: This study was performed to develop an algorithm using polymorphisms of CYP2D6, p-gp, OPRM1, COMT and psychological variables to predict tramadol response in Chinese patients recovering from upper limb fracture internal fixation surgery.	Tramadol	142-150	phosphoglycolate phosphatase	Homo sapiens	85-89
24624916-1	2014	AIM: This study was performed to develop an algorithm using polymorphisms of CYP2D6, p-gp, OPRM1, COMT and psychological variables to predict tramadol response in Chinese patients recovering from upper limb fracture internal fixation surgery.	Tramadol	142-150	opioid receptor mu 1	Homo sapiens	91-96
24624916-1	2014	AIM: This study was performed to develop an algorithm using polymorphisms of CYP2D6, p-gp, OPRM1, COMT and psychological variables to predict tramadol response in Chinese patients recovering from upper limb fracture internal fixation surgery.	Tramadol	142-150	catechol-O-methyltransferase	Homo sapiens	98-102
24157594-0	2014	Depressing interleukin-1beta contributed to the synergistic effects of tramadol and minocycline on spinal nerve ligation-induced neuropathic pain.	Tramadol	71-79	interleukin 1 beta	Homo sapiens	11-28
24157594-4	2014	Therefore, the present research is to confirm whether spinal IL-1beta-related pathway response contributes to the synergistic effects of tramadol and minocycline on SNL-induced neuropathic pain.	Tramadol	137-145	interleukin 1 beta	Homo sapiens	61-69
24157594-5	2014	Real-time RT-PCR demonstrated IL-1beta up-expression in the ipsilateral spinal dorsal horn 3 days after lesion, which could be significantly decreased by tramadol and minocycline coadministration.	Tramadol	154-162	interleukin 1 beta	Homo sapiens	30-38
24157594-6	2014	Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication.	Tramadol	136-144	mitogen-activated protein kinase 14	Homo sapiens	89-92
24157594-6	2014	Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication.	Tramadol	136-144	mitogen-activated protein kinase 14	Homo sapiens	96-99
24157594-9	2014	These results suggest that depressing SNL-induced aberrant activation of the spinal dorsal horn IL-1beta-related pathway contributes to the underlying mechanism of the synergistic effects of tramadol and minocycline coadministration on SNL-induced neuropathic mechanical allodynia.	Tramadol	191-199	interleukin 1 beta	Homo sapiens	96-104
22964922-3	2013	MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome behaviors, and these behavioral responses were highly exaggerated following 5-HTP or tramadol versus baseline and wild-type (WT) littermates.	Tramadol	149-157	monoamine oxidase A	Mus musculus	0-4
23922447-11	2013	It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin.	Tramadol	224-232	HNF1 homeobox A	Homo sapiens	95-99
23524988-10	2013	For refractory RLS, the choice is to change to gabapentin or a different dopamine agonist, addition of a second agent like gabapentin or benzodiazepine to the existing drug or changing to a high-potency opioid or tramadol.	Tramadol	213-221	RLS1	Homo sapiens	15-18
24009718-11	2013	Real-time RT-PCR demonstrated IL-1beta up-expression in the ipsilateral spinal dorsal horn after the lesion, which was significantly decreased by tramadol and propentofylline coadministration.	Tramadol	146-154	interleukin 1 beta	Rattus norvegicus	30-38
24009718-12	2013	Inhibiting proinflammatory factor IL-1beta contributed to the synergistic effects of tramadol and propentofylline coadministration on rat peripheral nerve injury-induced neuropathic pain.	Tramadol	85-93	interleukin 1 beta	Rattus norvegicus	34-42
23242004-1	2013	PURPOSE: Tramadol is mainly metabolized by the cytochrome P450 (CYP) 2D6, CYP2B6 and CYP3A4 enzymes.	Tramadol	9-17	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	74-80
23242004-1	2013	PURPOSE: Tramadol is mainly metabolized by the cytochrome P450 (CYP) 2D6, CYP2B6 and CYP3A4 enzymes.	Tramadol	9-17	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	85-91
23433451-5	2013	Propranolol significantly reversed the inhibitory effect of 100 mum tramadol on KCl-induced myometrial contractility but not that of 300 mum tramadol.	Tramadol	68-76	latexin	Homo sapiens	64-67
23588782-6	2013	CYP2D6 polymorphism influences the analgesic response to prodrug opioids (codeine, tramadol and oxycodone).	Tramadol	83-91	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
23428887-0	2013	Spectroscopic investigations of the interactions of tramadol hydrochloride and 5-azacytidine drugs with human serum albumin and human hemoglobin proteins.	Tramadol	52-74	albumin	Homo sapiens	116-123
23428887-1	2013	The interactions of tramadol hydrochloride (THC) and 5-azacytidine (AZA) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins were investigated by fluorescence, UV absorption and circular dichroism (CD) spectroscopy at pH 7.4 and different temperatures.	Tramadol	20-42	albumin	Homo sapiens	96-103
23428887-8	2013	The binding of THC-HSA and HMG proteins was spontaneous and exothermic.	Tramadol	15-18	albumin	Homo sapiens	19-22
23428887-10	2013	The results of CD analysis revealed that the addition of THC led to a significant conformational change in the secondary structure of HSA protein, on the contrary to HMG protein.	Tramadol	57-60	albumin	Homo sapiens	134-137
23428887-1	2013	The interactions of tramadol hydrochloride (THC) and 5-azacytidine (AZA) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins were investigated by fluorescence, UV absorption and circular dichroism (CD) spectroscopy at pH 7.4 and different temperatures.	Tramadol	20-42	albumin	Homo sapiens	105-108
23428887-1	2013	The interactions of tramadol hydrochloride (THC) and 5-azacytidine (AZA) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins were investigated by fluorescence, UV absorption and circular dichroism (CD) spectroscopy at pH 7.4 and different temperatures.	Tramadol	44-47	albumin	Homo sapiens	96-103
23428887-1	2013	The interactions of tramadol hydrochloride (THC) and 5-azacytidine (AZA) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins were investigated by fluorescence, UV absorption and circular dichroism (CD) spectroscopy at pH 7.4 and different temperatures.	Tramadol	44-47	albumin	Homo sapiens	105-108
23124884-0	2012	Tramadol reinforces antidepressant effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase B in rat hippocampus.	Tramadol	0-8	brain-derived neurotrophic factor	Rattus norvegicus	80-113
23212934-10	2012	Tramadol is metabolized through CYP2D6 enzymes and all SSRIs are inhibitors of these enzymes.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	32-38
23212934-11	2012	Inhibitors of CYP2D6 can increase the concentration of tramadol in the blood and thus increase its effects on serotonin in the brain, contributing to the development of serotonin syndrome.	Tramadol	55-63	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
23124884-0	2012	Tramadol reinforces antidepressant effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase B in rat hippocampus.	Tramadol	0-8	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	118-146
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	brain-derived neurotrophic factor	Rattus norvegicus	0-33
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	brain-derived neurotrophic factor	Rattus norvegicus	35-39
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	90-118
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	120-124
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	brain-derived neurotrophic factor	Rattus norvegicus	168-172
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	brain-derived neurotrophic factor	Rattus norvegicus	168-172
23124884-2	2012	Brain-derived neurotrophic factor (BDNF) is an important biomarker for mood disorders and tropomyosin-related kinase B (TrkB) is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.	Tramadol	194-202	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	322-326
23124884-6	2012	However, pretreatment with tramadol (5 mg/kg) enhanced the ketamine (10 mg/kg) -elicited antidepressant effects and upregulated the BDNF and TrkB levels in hippocampus.	Tramadol	27-35	brain-derived neurotrophic factor	Rattus norvegicus	132-136
23124884-6	2012	However, pretreatment with tramadol (5 mg/kg) enhanced the ketamine (10 mg/kg) -elicited antidepressant effects and upregulated the BDNF and TrkB levels in hippocampus.	Tramadol	27-35	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	141-145
23124884-7	2012	In conclusion, tramadol pretreatment reinforces the ketamine-elicited antidepressant effects, which is associated with the increased levels of BDNF and TrkB in rat hippocampus.	Tramadol	15-23	brain-derived neurotrophic factor	Rattus norvegicus	143-147
23124884-7	2012	In conclusion, tramadol pretreatment reinforces the ketamine-elicited antidepressant effects, which is associated with the increased levels of BDNF and TrkB in rat hippocampus.	Tramadol	15-23	neurotrophic receptor tyrosine kinase 2	Rattus norvegicus	152-156
22369095-0	2012	Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients.	Tramadol	30-38	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
23030000-1	2012	Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf).	Tramadol	221-229	transferrin	Mus musculus	310-321
23030000-1	2012	Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf).	Tramadol	221-229	transferrin	Mus musculus	323-325
23030000-1	2012	Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf).	Tramadol	221-229	lactotransferrin	Mus musculus	331-342
23030000-1	2012	Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf).	Tramadol	221-229	lactotransferrin	Mus musculus	344-346
23030000-2	2012	Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker.	Tramadol	17-25	transferrin	Mus musculus	102-104
23030000-2	2012	Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker.	Tramadol	17-25	lactotransferrin	Mus musculus	109-111
23030000-8	2012	Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.	Tramadol	99-107	transferrin	Mus musculus	26-28
23030000-8	2012	Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.	Tramadol	99-107	lactotransferrin	Mus musculus	43-45
22369095-4	2012	We aimed to investigate the effect of methadone on the pathways of tramadol metabolism: O-demethylation (CYP2D6) to the opioid-active metabolite M1 and N-demethylation (CYP3A4) to M2 in subjects maintained on methadone or buprenorphine as a control.	Tramadol	67-75	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	105-111
22369095-4	2012	We aimed to investigate the effect of methadone on the pathways of tramadol metabolism: O-demethylation (CYP2D6) to the opioid-active metabolite M1 and N-demethylation (CYP3A4) to M2 in subjects maintained on methadone or buprenorphine as a control.	Tramadol	67-75	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	169-175
22369095-8	2012	AIMS: To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects.	Tramadol	95-103	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	25-31
22369095-8	2012	AIMS: To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects.	Tramadol	95-103	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	50-56
22369095-8	2012	AIMS: To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects.	Tramadol	95-103	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	151-157
22369095-14	2012	CONCLUSIONS: Methadone inhibited the CYP2D6-mediated metabolism of tramadol to M1.	Tramadol	67-75	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	37-43
22039821-10	2012	Furthermore, the CDOCKER algorithm was further applied to study the impact of mutations of 28 active site residues (mostly non-conserved) of CYP2D6 on substrate binding modes using five probe substrates including bufuralol, debrisoquine, dextromethorphan, sparteine, and tramadol.	Tramadol	271-279	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	141-147
23061278-8	2012	The AChE activity levels also showed a simultaneous increase at 48 and 72 h, presumably to balance the increase in ACh levels on longer treatment with tramadol.	Tramadol	151-159	acetylcholinesterase	Rattus norvegicus	4-8
22452458-3	2012	Some interesting avenues of research require further pursuit- including evidence of cytochrome P450 2D6 (CYP2D6) induction during pregnancy and its effect on the generation of the active opioid metabolites morphine, oxymorphone, O-desmethyltramadol, and hydromorphone following the administration of codeine, oxycodone, tramadol, and hydrocodone respectively.	Tramadol	240-248	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	84-103
22698264-4	2012	Tramadol"s analgesia derives from relatively weak micro-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration.	Tramadol	0-8	opioid receptor mu 1	Homo sapiens	50-71
22452458-3	2012	Some interesting avenues of research require further pursuit- including evidence of cytochrome P450 2D6 (CYP2D6) induction during pregnancy and its effect on the generation of the active opioid metabolites morphine, oxymorphone, O-desmethyltramadol, and hydromorphone following the administration of codeine, oxycodone, tramadol, and hydrocodone respectively.	Tramadol	240-248	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	105-111
22698264-4	2012	Tramadol"s analgesia derives from relatively weak micro-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration.	Tramadol	0-8	opioid receptor mu 1	Homo sapiens	73-76
22698264-4	2012	Tramadol"s analgesia derives from relatively weak micro-opioid receptor (MOR) agonism, plus norepinephrine and serotonin reuptake inhibition, provided collectively by the enantiomers of the parent drug and a metabolite that is a stronger MOR agonist, but has lower CNS penetration.	Tramadol	0-8	opioid receptor mu 1	Homo sapiens	238-241
22428763-0	2012	Tramadol efficacy in patients with postoperative pain in relation to CYP2D6 and MDR1 polymorphisms.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	69-75
22694279-4	2012	Opioids metabolized by CYP2D6 include codeine, tramadol, hydrocodone, and oxycodone.	Tramadol	47-55	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	23-29
29776262-1	2012	AIM: The aim of this study was to investigate the associations between the CYP2D6*4 polymorphism, interindividual differences in CYP2D6 activity and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol.	Tramadol	221-229	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	75-81
29776262-1	2012	AIM: The aim of this study was to investigate the associations between the CYP2D6*4 polymorphism, interindividual differences in CYP2D6 activity and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol.	Tramadol	221-229	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	129-135
22533391-11	2012	Plasma concentrations of tumor necrosis factor-alpha and thromboxane B(2) were significantly reduced with tramadol-ketamine treatment but not with tramadol alone.	Tramadol	106-114	tumor necrosis factor	Equus caballus	25-52
22533391-11	2012	Plasma concentrations of tumor necrosis factor-alpha and thromboxane B(2) were significantly reduced with tramadol-ketamine treatment but not with tramadol alone.	Tramadol	147-155	tumor necrosis factor	Equus caballus	25-52
21971437-11	2012	The duration of analgesia was significantly longer in Groups TPN and TIM, where tramadol was administered, either i.m.	Tramadol	80-88	Rho guanine nucleotide exchange factor 5	Homo sapiens	69-72
22428763-0	2012	Tramadol efficacy in patients with postoperative pain in relation to CYP2D6 and MDR1 polymorphisms.	Tramadol	0-8	ATP binding cassette subfamily B member 1	Homo sapiens	80-84
22428763-1	2012	OBJECTIVES: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy.	Tramadol	118-126	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	59-65
22428763-1	2012	OBJECTIVES: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy.	Tramadol	118-126	ATP binding cassette subfamily B member 1	Homo sapiens	70-74
22428763-2	2012	BACKGROUND: Pharmacokinetics of tramadol and its metabolites is stereoselective and displays high interindividual variability correlating with polymorphic CYP2D6 in the population.	Tramadol	32-40	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	155-161
22428763-3	2012	Available data provide controversial results regarding the analgesic efficacy of tramadol in subjects with different CYP2D6 genotypes.	Tramadol	81-89	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	117-123
22428763-12	2012	CONCLUSION: CYP2D6 plays a significant role in tramadol analgesic efficacy.	Tramadol	47-55	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	12-18
22577289-0	2012	Tramadol pretreatment enhances ketamine-induced antidepressant effects and increases mammalian target of rapamycin in rat hippocampus and prefrontal cortex.	Tramadol	0-8	mechanistic target of rapamycin kinase	Homo sapiens	85-114
22148986-6	2012	CYP2D6 catabolizes O-demethylation of codeine, tramadol, oxycodone, and hydrocodone to more potent metabolites.	Tramadol	47-55	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	0-6
22577289-9	2012	More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex.	Tramadol	36-44	mechanistic target of rapamycin kinase	Rattus norvegicus	132-136
22577289-10	2012	Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.	Tramadol	18-26	mechanistic target of rapamycin kinase	Rattus norvegicus	134-138
21562485-7	2011	In conclusion, polymorphisms in OCT1 influence the pharmacokinetics of O-desmethyltramadol, presumably by affecting its uptake into liver cells, and thus may modulate the efficacy of tramadol treatment.	Tramadol	82-90	solute carrier family 22 member 1	Homo sapiens	32-36
23331900-1	2012	PURPOSE: Tramadol Hydrochloride is a widely-used centrally acting analgesic drug, which has some features of being a P-gp substrate.	Tramadol	9-31	phosphoglycolate phosphatase	Rattus norvegicus	117-121
23331900-2	2012	The present study evaluates the functional involvement of P-gp in CNS distribution of tramadol.	Tramadol	86-94	phosphoglycolate phosphatase	Rattus norvegicus	58-62
23331900-3	2012	METHODS: The possible involvement of P-glycoprotein in brain distribution of tramadol was evaluated using a pharmacokinetic approach in two groups of Pgp-inhibited and control rats.	Tramadol	77-85	ATP-binding cassette, subfamily B (MDR/TAP), member 1B	Rattus norvegicus	37-51
23331900-5	2012	RESULTS: The brain uptake clearances of tramadol in Pgp-inhibited and control rats were 2.47+-0.56 and 2.34+-0.56 ml min(-1)g(-1), respectively, for 1 mg/kg and 3.50+-0.60 and 3.14+-1.02 mlmin(-1)g(-1), respectively, for 10 mg/kg dose.	Tramadol	40-48	phosphoglycolate phosphatase	Rattus norvegicus	52-55
22778699-4	2012	Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, beta-endorphin levels, and interleukin 6 (IL-6) levels.	Tramadol	0-8	interleukin 6	Canis lupus familiaris	171-184
22778699-4	2012	Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, beta-endorphin levels, and interleukin 6 (IL-6) levels.	Tramadol	0-8	interleukin 6	Canis lupus familiaris	186-190
21999760-5	2011	Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects.	Tramadol	136-144	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	60-75
21999760-5	2011	Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects.	Tramadol	136-144	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	77-83
22393585-0	2011	[The expression of GABA(A) receptor alpha1 and GABA(B) receptor 1 in medulla oblongata solitary nucleus and ambiguous nucleus in the cases of tramadol intoxication].	Tramadol	142-150	gamma-aminobutyric acid type A receptor subunit alpha1	Homo sapiens	19-42
22393585-1	2011	OBJECTIVE: To observe the expression of GABA(A) receptor alpha1 (GABA(A)alpha1) and GABA(B) receptor 1 (GABA(B)1) in human medulla oblongata solitary nucleus and ambiguous nucleus due to tramadol-induced death.	Tramadol	187-195	gamma-aminobutyric acid type A receptor subunit alpha1	Homo sapiens	40-63
22393585-1	2011	OBJECTIVE: To observe the expression of GABA(A) receptor alpha1 (GABA(A)alpha1) and GABA(B) receptor 1 (GABA(B)1) in human medulla oblongata solitary nucleus and ambiguous nucleus due to tramadol-induced death.	Tramadol	187-195	gamma-aminobutyric acid type A receptor subunit alpha1	Homo sapiens	65-78
22393585-2	2011	METHODS: GABA(A)alpha1 and GABA(B)1 were detected by immunohistochemical SP method in tramadol-induced death group and control group.	Tramadol	86-94	gamma-aminobutyric acid type A receptor subunit alpha1	Homo sapiens	9-22
22393585-5	2011	In cases of tramadol-induced death, the expression of GABA(A)alpha1 and GABA(B)1 significantly increased.	Tramadol	12-20	gamma-aminobutyric acid type A receptor subunit alpha1	Homo sapiens	54-67
22393585-6	2011	CONCLUSION: The mechanism of tramadol intoxication death could be caused by respiratory depression induced by over-expression of GABA(A)alpha1 and GABA(B)1 in medulla oblongata solitary nucleus and ambiguous nucleus.	Tramadol	29-37	gamma-aminobutyric acid type A receptor subunit alpha1	Homo sapiens	129-142
21691803-0	2011	Near-fatal tramadol cardiotoxicity in a CYP2D6 ultrarapid metabolizer.	Tramadol	11-19	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	40-46
21691803-2	2011	The marketed tramadol is a racemic mixture containing 50% (+)tramadol and 50% (-)tramadol and is mainly metabolized to O-desmethyltramadol (M1) by the cytochrome P450 CYP2D6.	Tramadol	13-21	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	167-173
21691803-2	2011	The marketed tramadol is a racemic mixture containing 50% (+)tramadol and 50% (-)tramadol and is mainly metabolized to O-desmethyltramadol (M1) by the cytochrome P450 CYP2D6.	Tramadol	61-69	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	167-173
21691803-2	2011	The marketed tramadol is a racemic mixture containing 50% (+)tramadol and 50% (-)tramadol and is mainly metabolized to O-desmethyltramadol (M1) by the cytochrome P450 CYP2D6.	Tramadol	61-69	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	167-173
21691803-7	2011	Genotyping of CYP2D6 revealed the patient to be heterozygous for a duplicated wild-type allele, predictive of a CYP2D6 ultrarapid metabolizer (UM) phenotype, confirmed by calculation of the tramadol/M1 (MR1) metabolic ratio at all time points.	Tramadol	190-198	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	14-20
21691803-7	2011	Genotyping of CYP2D6 revealed the patient to be heterozygous for a duplicated wild-type allele, predictive of a CYP2D6 ultrarapid metabolizer (UM) phenotype, confirmed by calculation of the tramadol/M1 (MR1) metabolic ratio at all time points.	Tramadol	190-198	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	112-118
21691803-9	2011	Because of the inhibition of norepinephrine reuptake, excessive blood epinephrine levels in this CYP2D6R UM patient following excessive tramadol ingestion could explain the observed strong myocardial stunning.	Tramadol	136-144	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	97-103
21729116-1	2011	WHAT IS KNOWN AND OBJECTIVE: The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6.	Tramadol	50-58	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	176-182
21562485-0	2011	Genetically polymorphic OCT1: another piece in the puzzle of the variable pharmacokinetics and pharmacodynamics of the opioidergic drug tramadol.	Tramadol	136-144	solute carrier family 22 member 1	Homo sapiens	24-28
21562485-1	2011	We investigated whether tramadol or its active metabolite, O-desmethyltramadol, are substrates of the organic cation transporter OCT1 and whether polymorphisms in OCT1 affect tramadol and O-desmethyltramadol pharmacokinetics.	Tramadol	70-78	solute carrier family 22 member 1	Homo sapiens	129-133
20354688-0	2010	Two separate dose-dependent effects of paroxetine: mydriasis and inhibition of tramadol"s O-demethylation via CYP2D6.	Tramadol	79-87	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	110-116
21215785-5	2011	The K(i) values obtained ranged from 0.1380 nM (sufentanil) to 12.486 muM (tramadol).	Tramadol	75-83	latexin	Homo sapiens	70-73
20723094-2	2011	BACKGROUND: Tramadol (M) is metabolized by O-demethylation (cytochrome P450 [CYP] 2D6) to the pharmacodynamic active metabolite O-demethyl tramadol (M1).	Tramadol	12-20	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	60-85
20709477-4	2010	Polymorphisms of the cytochrome P 450 2D6 influence the metabolism of many drugs including the analgesics codeine, tramadol, hydrocodone and oxycodone, as well as the metabolism of tricyclic antidepressants and the anticancer drug tamoxifen.	Tramadol	115-123	cytochrome P450 2D6	Homo sapiens	21-41
21140323-4	2010	This genetic situation caused a quick metabolizing-status for substances dependent on CYP2D6 like Tramadol, which is a prodrug.	Tramadol	98-106	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	86-92
20444752-0	2010	Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants.	Tramadol	43-51	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	68-74
20444752-0	2010	Adverse events in analgesic treatment with tramadol associated with CYP2D6 extensive-metaboliser and OPRM1 high-expression variants.	Tramadol	43-51	opioid receptor mu 1	Homo sapiens	101-106
20504256-3	2010	Polymorphisms of the cytochrome P450 enzymes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone and tricyclic antidepressants.	Tramadol	87-95	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	46-52
20662312-0	2010	Preparation and characterization of tramadol PEG-coated multivesicular liposomes for sustained release.	Tramadol	36-44	progestagen associated endometrial protein	Homo sapiens	45-48
20662312-7	2010	Tramadol was continuously released from MVL formulations in PBS (pH 6.8) in vitro, and reached a maximum of 80% within 72 h. The results show that tramadol PEG-coated MVLs could provide sustained release according to the first order kinetic equation.	Tramadol	0-8	progestagen associated endometrial protein	Homo sapiens	156-159
20662312-7	2010	Tramadol was continuously released from MVL formulations in PBS (pH 6.8) in vitro, and reached a maximum of 80% within 72 h. The results show that tramadol PEG-coated MVLs could provide sustained release according to the first order kinetic equation.	Tramadol	147-155	progestagen associated endometrial protein	Homo sapiens	156-159
20456744-0	2010	Relationship of CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers.	Tramadol	73-81	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	16-22
20175977-10	2010	TTMP was significantly better for tramadol/acetaminophen and naproxen than placebo (P&lt;0.001 to P=0.015) for walks on Day 1 after a single dose and on Day 3.	Tramadol	34-42	chromosome 3 open reading frame 52	Homo sapiens	0-4
20456744-1	2010	OBJECTIVE: To investigate the relationship between CYP2D6 genetic polymorphisms and the pharmacokinetics of tramadol in Chinese volunteers.	Tramadol	108-116	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	51-57
20016246-0	2010	Evidence for the involvement of glutamatergic and neurokinin 1 receptors in the antinociception elicited by tramadol in mice.	Tramadol	108-116	tachykinin 1	Mus musculus	50-62
20194144-8	2010	Patients who lack cytochrome P450 2D6 isoenzyme activity are prone to adverse effects of TCAs and venlafaxine and have a weaker analgesic response to tramadol.	Tramadol	150-158	cytochrome P450 2D6	Homo sapiens	18-37
20012267-0	2010	Tramadol-induced seizurogenic effect: a possible role of opioid-dependent histamine H1 receptor activation-linked mechanism.	Tramadol	0-8	histamine receptor H1	Mus musculus	74-95
20305307-6	2010	The reason of this effect is that tramadol is the substrate and clarithromycin is the inhibitor of the CYP 3A4 enzyme.	Tramadol	34-42	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	103-110
19477145-5	2010	The opioid antagonist naloxone partially reversed the tramadol-induced LEP amplitude decrease.	Tramadol	54-62	leptin	Homo sapiens	71-74
20016246-1	2010	This study was designed to evaluate the role of spinal glutamatergic receptors and neurokinin 1-mediated pathway in the antinociception elicited by tramadol in mice.	Tramadol	148-156	tachykinin 1	Mus musculus	83-95
19710642-0	2009	Escitalopram is a weak inhibitor of the CYP2D6-catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain.	Tramadol	76-88	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	40-46
19710642-1	2009	Tramadol is O-demethylated to the active metabolite (+)-O-desmethyltramadol ((+)-M1) via CYP2D6, an enzyme that is weakly inhibited by escitalopram.	Tramadol	0-8	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	89-95
19496778-0	2009	Uptake/efflux transport of tramadol enantiomers and O-desmethyl-tramadol: focus on P-glycoprotein.	Tramadol	27-35	ATP binding cassette subfamily B member 1	Homo sapiens	83-97
19665424-2	2009	The solid inclusion complex of tramadol with beta-CD is investigated by FT-IR, (1)H NMR, scanning electron microscope (SEM), DSC and semiempirical methods.	Tramadol	31-39	desmocollin 3	Homo sapiens	125-128
19693978-0	2009	[Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats].	Tramadol	1-9	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	19-24
19275775-0	2009	Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice.	Tramadol	0-8	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	163-184
19275775-0	2009	Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice.	Tramadol	0-8	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	186-190
19275775-5	2009	Here we show that tramadol and meperidine, but not morphine, induce serotonin syndrome-like behaviours in mice, and we show that this response is exaggerated in mice lacking one or two copies of SERT.	Tramadol	18-26	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	195-199
19275775-6	2009	The exaggerated response to tramadol in SERT-/- mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635.	Tramadol	28-36	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	40-44
19275775-6	2009	The exaggerated response to tramadol in SERT-/- mice was blocked by pretreatment with the 5-HT1A antagonist WAY 100635.	Tramadol	28-36	5-hydroxytryptamine (serotonin) receptor 1A	Mus musculus	90-96
19275775-7	2009	Further, we show that morphine-, meperidine- and tramadol-induced analgesia is markedly decreased in SERT-/- mice.	Tramadol	49-57	solute carrier family 6 (neurotransmitter transporter, serotonin), member 4	Mus musculus	101-105
19693978-10	2009	The greatest density of Fos-positive neurons was located in lamine I-II in Group I. Serum IL-6 levels were significantly elevated in Group I. Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1.	Tramadol	160-168	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	213-218
19693978-10	2009	The greatest density of Fos-positive neurons was located in lamine I-II in Group I. Serum IL-6 levels were significantly elevated in Group I. Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1.	Tramadol	160-168	interleukin 6	Rattus norvegicus	240-244
19693978-11	2009	Administration of tramadol postoperatively also suppressed the c-fos expression and serum IL-6 production as showed in PT10 but were weaker than those in Group T10.	Tramadol	18-26	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	63-68
19693978-11	2009	Administration of tramadol postoperatively also suppressed the c-fos expression and serum IL-6 production as showed in PT10 but were weaker than those in Group T10.	Tramadol	18-26	interleukin 6	Rattus norvegicus	90-94
19693978-12	2009	CONCLUSION: Pretreatment with tramadol can produce dose-dependent inhibitory effect on c-fos expression in spinal cord dorsal horn and then suppress the inflammatory response to the trauma.	Tramadol	30-38	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	87-92
19693978-0	2009	[Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats].	Tramadol	1-9	interleukin 6	Rattus norvegicus	73-77
19693978-1	2009	OBJECTIVE: To investigate effect of tramadol on c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats.	Tramadol	36-44	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	48-53
19693978-10	2009	The greatest density of Fos-positive neurons was located in lamine I-II in Group I. Serum IL-6 levels were significantly elevated in Group I. Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1.	Tramadol	160-168	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	24-27
19693978-10	2009	The greatest density of Fos-positive neurons was located in lamine I-II in Group I. Serum IL-6 levels were significantly elevated in Group I. Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1.	Tramadol	160-168	interleukin 6	Rattus norvegicus	90-94
19488542-8	2009	RESULTS: The concentration of TNF-+/- before (5.8 +/- 2.8 pg.mL-(1)) was significantly higher than after treatment with tramadol (4.8 +/- 2.1 pg.mL-1; p = 0.04, Mann-Whitney test).	Tramadol	120-128	tumor necrosis factor	Homo sapiens	30-33
19539101-0	2009	N-of-1 double-blind, randomized controlled trial of tramadol to treat chronic cough.	Tramadol	52-60	mitochondrial ribosomal protein L49	Homo sapiens	0-6
19539101-4	2009	METHODS: This was an N-of-1 double-blind, randomized controlled trial of tramadol against placebo.	Tramadol	73-81	mitochondrial ribosomal protein L49	Homo sapiens	21-27
19488542-12	2009	Plasma levels of TNF-+/-, but not of IL-6, sTNF-R, and IL-1(2), decreased after treatment with tramadol (100 mg every 12 hours).	Tramadol	95-103	tumor necrosis factor	Homo sapiens	17-20
19288949-0	2009	Tramadol overdose induced seizure, dramatic rise of CPK and acute renal failure.	Tramadol	0-8	phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha	Homo sapiens	52-55
19902987-13	2009	Genetically caused inactivity of CYP2D6 renders codeine ineffective owing to lack of morphine formation, decreases the efficacy of tramadol owing to reduced formation of the active O-desmethyl-tramadol and reduces the clearance of methadone.	Tramadol	131-139	cytochrome P450 family 2 subfamily D member 6	Homo sapiens	33-39