PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
29430193-2	2018	Tolvaptan, a selective vasopressin V2 receptor antagonist, delays the increase in kidney volume (a surrogate marker for disease progression), slows the decline in renal function, and reduces pain in ADPKD patients with relatively preserved renal function.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	23-46
29311539-1	2018	BACKGROUND Tolvaptan, an antagonist of the vasopressin V2 receptor is a novel oral diuretic that promotes water excretion selectively.	Tolvaptan	11-20	arginine vasopressin receptor 2	Homo sapiens	43-66
29029277-0	2018	miR-122 Release in Exosomes Precedes Overt Tolvaptan-Induced Necrosis in a Primary Human Hepatocyte Micropatterned Coculture Model.	Tolvaptan	43-52	microRNA 122	Homo sapiens	0-7
29029277-7	2018	Taken together, these data suggest that tolvaptan treatment induces cellular stress and exosome release of miR-122 in primary human hepatocytes in the absence of overt necrosis, providing direct demonstration of this with a drug capable of causing IDILI.	Tolvaptan	40-49	microRNA 122	Homo sapiens	107-114
30347391-3	2018	A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice.	Tolvaptan	249-258	deoxynucleotidyltransferase terminal interacting protein 2	Homo sapiens	198-202
30347391-10	2018	CONCLUSIONS: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan.	Tolvaptan	165-174	deoxynucleotidyltransferase terminal interacting protein 2	Homo sapiens	32-36
29311539-9	2018	The time from hANP initiation to discontinuation and the time to removal of central vein catheters were significantly reduced in tolvaptan-treated patients.	Tolvaptan	129-138	natriuretic peptide A	Homo sapiens	14-18
28759864-7	2017	Our data show that tolvaptan is metabolized to at least 20 phase I metabolites, the biotransformation reactions being catalyzed mainly by CYP3A4 and CYP3A5 isoforms.	Tolvaptan	19-28	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	138-144
29399022-2	2017	Tolvaptan is a selective vasopressin V2 receptor antagonist that produces effective aquaresis, and its use in ALS patients has not been previously reported.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	25-48
29105594-1	2017	BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, >=60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels.	Tolvaptan	210-219	arginine vasopressin receptor 2	Homo sapiens	175-198
28943585-2	2017	The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level.	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	4-27
29154417-10	2017	Tolvaptan is effective in treating CS2 or CS3 ADHF patients who present fluid retention and congestion, suggesting its potential efficacy for fluid management in the ADHF patients with CKD without worsening the renal function.	Tolvaptan	0-9	chorionic somatomammotropin hormone 2	Homo sapiens	35-38
29154417-10	2017	Tolvaptan is effective in treating CS2 or CS3 ADHF patients who present fluid retention and congestion, suggesting its potential efficacy for fluid management in the ADHF patients with CKD without worsening the renal function.	Tolvaptan	0-9	myozenin 3	Homo sapiens	42-45
29204517-2	2018	The cyst development is attenuated by a vasopressin V2 receptor antagonist tolvaptan which, however, will not affect proximal tubule cysts devoid of V2 receptor.	Tolvaptan	75-84	arginine vasopressin receptor 2	Homo sapiens	40-63
28759864-7	2017	Our data show that tolvaptan is metabolized to at least 20 phase I metabolites, the biotransformation reactions being catalyzed mainly by CYP3A4 and CYP3A5 isoforms.	Tolvaptan	19-28	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	149-155
28905441-5	2017	On the basis of recent clinical data, the blockade of V2 vasopressin receptors using tolvaptan in patients with rapidly progressing ADPKD has been granted in several countries, and a long-term randomized trial evaluating the effect of an increase in water intake in patients with CKD is on-going.	Tolvaptan	85-94	arginine vasopressin	Homo sapiens	57-68
28326667-0	2017	The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment.	Tolvaptan	27-36	aquaporin 2	Homo sapiens	75-79
28326667-1	2017	Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	23-34
28326667-5	2017	In MDCK, tolvaptan prevented dDAVP-induced increase in ser256-AQP2 and osmotic water permeability.	Tolvaptan	9-18	aquaporin 2	Homo sapiens	62-66
28326667-9	2017	Consistent with this finding, tolvaptan partially reduced the increase in ser256-AQP2 and the water permeability in response to forskolin, a direct activator of adenylyl cyclase (AC), suggesting that the increase in intracellular calcium is associated with an inhibition of the calcium-inhibitable AC type VI.	Tolvaptan	30-39	aquaporin 2	Homo sapiens	81-85
28326667-10	2017	Furthermore, tolvaptan treatment reduced AQP2 excretion in two SIAD patients and normalized plasma sodium concentration.	Tolvaptan	13-22	aquaporin 2	Homo sapiens	41-45
28326667-11	2017	These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of tolvaptan and underscore a novel effect in raising intracellular calcium that can be of significant clinical relevance.	Tolvaptan	118-127	aquaporin 2	Homo sapiens	77-81
28810844-1	2017	BACKGROUND: Tolvaptan slows progression of autosomal dominant polycystic kidney disease (ADPKD) by antagonizing the vasopressin-cAMP axis.	Tolvaptan	12-21	arginine vasopressin	Homo sapiens	116-127
27448501-0	2017	Efficacy of vasopressin V2 receptor antagonist tolvaptan in treatment of hepatic edema.	Tolvaptan	47-56	arginine vasopressin receptor 2	Homo sapiens	12-35
28810844-12	2017	The reduced GFR during tolvaptan most likely is caused by the reduction in extracellular fluid volume and blood pressure.	Tolvaptan	23-32	Rap guanine nucleotide exchange factor 5	Homo sapiens	12-15
28218410-1	2017	In the pivotal TEMPO 3:4 trial, the arginine vasopressin V2-receptor antagonist tolvaptan reduced the rate of kidney growth in patients with autosomal dominant polycystic kidney disease.	Tolvaptan	80-89	arginine vasopressin receptor 2	Homo sapiens	45-68
27670393-1	2017	AIM: The vasopressin V2 receptor antagonist tolvaptan has been used for the treatment of cirrhotic patients with ascites; however, no predictor of efficacy and prognosis has been developed.	Tolvaptan	44-53	arginine vasopressin receptor 2	Homo sapiens	9-32
27704665-1	2017	AIMS: The efficacy of the vasopressin V2 receptor antagonist tolvaptan for difficult-to-treat cirrhotic ascites has recently been reported.	Tolvaptan	61-70	arginine vasopressin receptor 2	Homo sapiens	26-49
28751810-2	2017	Hence, combination therapy with tolvaptan, a vasopressin V2 receptor antagonist, has been approved in Japan.	Tolvaptan	32-41	arginine vasopressin receptor 2	Rattus norvegicus	45-68
27339446-1	2017	BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	25-48
27190355-0	2017	Tolvaptan suppresses monocyte chemotactic protein-1 excretion in autosomal-dominant polycystic kidney disease.	Tolvaptan	0-9	C-C motif chemokine ligand 2	Homo sapiens	21-51
27190355-4	2017	In a sub-analysis, we determined whether tolvaptan administration for up to 3 years changed the urinary excretion of MCP-1 referenced to creatinine in 869 treated subjects compared with 438 placebo subjects.	Tolvaptan	41-50	C-C motif chemokine ligand 2	Homo sapiens	117-122
27190355-10	2017	Conclusion: Tolvaptan, administered for 3 years to patients with ADPKD, caused a sustained reduction in the urinary excretion of MCP-1 relative to placebo.	Tolvaptan	12-21	C-C motif chemokine ligand 2	Homo sapiens	129-134
27448501-1	2017	AIM: Tolvaptan, an oral active vasopressin V2 receptor antagonist, is widely used for hepatic edema in Japan, but its clinical benefits have yet to be fully clarified.	Tolvaptan	5-14	arginine vasopressin receptor 2	Homo sapiens	31-54
27448501-6	2017	The assessment of predictive factors for response to tolvaptan showed that serum creatinine and C-reactive protein levels were important predictors of initial response, and that hepatic conditions, such as the Child-Pugh score or presence of hepatocellular carcinoma, as well as initial response, were significant predictors of long-term response.	Tolvaptan	53-62	C-reactive protein	Homo sapiens	96-114
28194574-3	2017	CASE DIAGNOSIS/TREATMENT: A female infant with massive renal enlargement, respiratory compromise and hyponatraemia was treated with the arginine vasopressin receptor 2 antagonist tolvaptan.	Tolvaptan	179-188	arginine vasopressin receptor 2	Homo sapiens	136-167
27920153-6	2017	The Uosm response to tolvaptan depended on baseline eGFR and Uosm.	Tolvaptan	21-30	epidermal growth factor receptor	Homo sapiens	52-56
27920153-11	2017	In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm.	Tolvaptan	134-143	epidermal growth factor receptor	Homo sapiens	96-100
27943449-1	2017	Tolvaptan (TF), a selective arginine vasopressin V2 receptor antagonist, was approved by the Food and Drug Administration in 2009.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	37-60
28194574-5	2017	CONCLUSION: Tolvaptan may be a useful treatment for severe neonatal PKD.	Tolvaptan	12-21	protein kinase D1	Homo sapiens	68-71
28115652-3	2017	Significant elevations in plasma alanine aminotransferase (ALT) were observed in tolvaptan-treated animals in 3 of the 45 strains.	Tolvaptan	81-90	glutamic--pyruvic transaminase	Homo sapiens	33-57
28251822-4	2017	Hyponatremic subjects with SIADH and cancer received the oral selective vasopressin V2-receptor antagonist tolvaptan (n = 12) or matching placebo (n = 16) once-daily for 30 days.	Tolvaptan	107-116	arginine vasopressin receptor 2	Homo sapiens	72-95
28302292-3	2017	OBJECTIVES: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response.	Tolvaptan	53-62	arginine vasopressin	Homo sapiens	148-159
27363974-6	2017	Recently, the newly produced diuretic, tolvaptan (vasopressin V2 receptor antagonist), was reported to be effective in the treatment of refractory ascites in liver cirrhosis; however, there has not been an associated positive effect on the prognosis.	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	50-73
28288570-1	2017	BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist.	Tolvaptan	12-21	arginine vasopressin	Homo sapiens	37-48
28288570-8	2017	Tolvaptan decreased u-ENaCgamma dose-dependently and increased p-AVP threefold, whereas u-AQP2 was unchanged.	Tolvaptan	0-9	sodium channel epithelial 1 subunit gamma	Homo sapiens	22-31
28166521-1	2017	BACKGROUND: In TEMPO 3:4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function.	Tolvaptan	65-74	arginine vasopressin receptor 2	Homo sapiens	30-53
28614813-4	2017	Treatment with vasopressin V2-receptor antagonist tolvaptan has been shown to inhibit disease progression in experimental studies, as well as in a large randomized controlled trial involving 1,445 patients with autosomal dominant PKD, lowering total kidney volume growth from 5.5 to 2.8%, and the slope of the reciprocal of the serum creatinine level from -3.81 to -2.61 mg per mL-1/year.	Tolvaptan	50-59	arginine vasopressin receptor 2	Homo sapiens	15-38
28090051-3	2017	Two distinct cases described herein illustrate the different effects of tolvaptan in responders and non-responders, according to the pre-treatment levels of AQP-2 immunostaining in the samples from renal biopsy and urinary levels of AQP-2 and osmolality, suggesting that these values may be useful predictors of response to tolvaptan in patients with nephrotic IMN.	Tolvaptan	72-81	aquaporin 2	Homo sapiens	157-162
27856088-1	2017	BACKGROUND: Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group.	Tolvaptan	169-178	arginine vasopressin receptor 2	Homo sapiens	182-205
28090051-3	2017	Two distinct cases described herein illustrate the different effects of tolvaptan in responders and non-responders, according to the pre-treatment levels of AQP-2 immunostaining in the samples from renal biopsy and urinary levels of AQP-2 and osmolality, suggesting that these values may be useful predictors of response to tolvaptan in patients with nephrotic IMN.	Tolvaptan	72-81	aquaporin 2	Homo sapiens	233-238
27655350-1	2017	Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	25-48
29145907-4	2017	This year, the vasopressin V2 receptor antagonist tolvaptan was approved for prescription in ADPKD, to slow the rate of renal function decline.	Tolvaptan	50-59	arginine vasopressin receptor 2	Homo sapiens	15-38
27395406-1	2016	PURPOSE: The long-term efficacy of tolvaptan, a vasopressin V2 receptor antagonist, has been reported.	Tolvaptan	35-44	arginine vasopressin receptor 2	Homo sapiens	48-71
27591907-1	2016	OBJECTIVE: To investigate the efficacy of the selective vasopressin V2-receptor antagonist tolvaptan in postoperative fluid management after cardiovascular surgery using cardiopulmonary bypass.	Tolvaptan	91-100	arginine vasopressin receptor 2	Homo sapiens	56-79
27020854-6	2016	In vivo, we measured the urinary excretion and tissue uptake of fluorescently loaded ECVs delivered systemically to mice before and after administration of the vasopressin V2 receptor antagonist tolvaptan.	Tolvaptan	195-204	arginine vasopressin receptor 2	Mus musculus	160-183
27404673-9	2016	Likewise, in patients whose eGFR was 30mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P=0.017) with a significant interaction (P value for interaction=0.015).	Tolvaptan	65-74	epidermal growth factor receptor	Homo sapiens	28-32
27404673-9	2016	Likewise, in patients whose eGFR was 30mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P=0.017) with a significant interaction (P value for interaction=0.015).	Tolvaptan	65-74	CD59 molecule (CD59 blood group)	Homo sapiens	42-47
27404696-10	2016	Increase in proximal tubular expression of aquaporin 1, Angiotensin II, and vasopressin seen with tolvaptan treatments were normalized to basal levels, similar to levels in placebo-treated mice.	Tolvaptan	98-107	aquaporin 1	Mus musculus	43-54
26676672-1	2016	Tolvaptan is an oral antagonist of arginine vasopressin receptor 2 that has been approved in Japan to reduce congestive symptoms in patients with heart failure refractory to loop diuretics.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	35-66
27921039-5	2016	Recently, the European Medicines Agency (EMA) approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency connected with ADPKD in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease.	Tolvaptan	105-114	arginine vasopressin receptor 2	Homo sapiens	70-93
27921039-25	2016	(3) The vasopressin 2 receptor antagonist tolvaptan was approved in Europe, Canada, Japan, and Korea to slow down progression of kidney disease in ADPKD patients.	Tolvaptan	42-51	arginine vasopressin	Homo sapiens	8-19
27628415-1	2016	The vasopressin type-2 antagonist tolvaptan (TLV) has clinical advantages including amelioration of congestion and normalization of hyponatremia in patients with decompensated heart failure (HF).	Tolvaptan	34-43	arginine vasopressin	Homo sapiens	4-15
27628415-1	2016	The vasopressin type-2 antagonist tolvaptan (TLV) has clinical advantages including amelioration of congestion and normalization of hyponatremia in patients with decompensated heart failure (HF).	Tolvaptan	45-48	arginine vasopressin	Homo sapiens	4-15
27540244-2	2016	Tolvaptan (Jinarc ) is a vasopressin V2-receptor antagonist licensed for use to slow the progression of cyst development and renal insufficiency of ADPKD in adults with CKD stage 1 to 3 with evidence of rapidly progressing disease.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	25-48
27818782-2	2016	We tested whether tolvaptan, a vasopressin V2-receptor antagonist, could reduce unfavourable furosemide-induced effects during CHF treatment.	Tolvaptan	18-27	arginine vasopressin receptor 2	Homo sapiens	31-54
27818782-11	2016	CONCLUSIONS: As compared with furosemide, tolvaptan in patients with acute heart failure is associated with comparable decongestion, better preservation of renal function and less activation of renin-angiotensin system.	Tolvaptan	42-51	renin	Homo sapiens	194-199
29142926-5	2016	The effects of tolvaptan on TKV and eGFR slopes were greater in classes 1C to E than in 1B.	Tolvaptan	15-24	epidermal growth factor receptor	Homo sapiens	36-40
29142926-6	2016	In TEMPO 3:4, tolvaptan reduced TKV and eGFR slopes from 5.51% to 2.80% per year and from -3.70 to -2.78 ml/min/1.73 m2 per year, and lowered the risk for a composite endpoint of clinical progression events (hazard ratio = 0.87).	Tolvaptan	14-23	epidermal growth factor receptor	Homo sapiens	40-44
30547521-0	2016	[Vasopressin antagonist (Tolvaptan)].	Tolvaptan	25-34	arginine vasopressin	Homo sapiens	1-12
27357439-0	2016	Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.	Tolvaptan	37-46	arginine vasopressin	Homo sapiens	166-177
27357439-3	2016	Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	29-40
27478876-8	2016	Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation.	Tolvaptan	120-129	aquaporin 2	Rattus norvegicus	91-102
27478876-8	2016	Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation.	Tolvaptan	120-129	aquaporin 2	Rattus norvegicus	104-108
27478876-8	2016	Metformin increased protein abundance of inner medullary urea transporter UT-A1 by 61% and aquaporin 2 (AQP2) by 44% in tolvaptan-treated rats, and immunohistochemistry showed increased membrane accumulation of AQP2 with acute and chronic AMPK stimulation.	Tolvaptan	120-129	aquaporin 2	Rattus norvegicus	211-215
26610908-0	2016	Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites.	Tolvaptan	97-106	aquaporin 2	Homo sapiens	25-50
26610908-3	2016	Tolvaptan, an antagonist of vasopressin type 2 receptor, inhibits water reabsorption in cirrhosis.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	28-39
26610908-4	2016	The aim of this study was to determine the correlation between the pharmacological effect of tolvaptan and the dynamics of urinary AQP2 levels.	Tolvaptan	93-102	aquaporin 2	Homo sapiens	131-135
26610908-8	2016	After administration of tolvaptan, urinary AQP2/creatinine ratios decreased by 45.0 % at 4 h and 77.0 % at 8 h. Similarly, urinary osmolarity decreased by 42.0 % at 4 h and 41.5 % at 8 h. Urinary AQP2 levels and urinary osmolarity significantly correlated at the baseline and at all time points after tolvaptan administration.	Tolvaptan	24-33	aquaporin 2	Homo sapiens	43-47
26610908-8	2016	After administration of tolvaptan, urinary AQP2/creatinine ratios decreased by 45.0 % at 4 h and 77.0 % at 8 h. Similarly, urinary osmolarity decreased by 42.0 % at 4 h and 41.5 % at 8 h. Urinary AQP2 levels and urinary osmolarity significantly correlated at the baseline and at all time points after tolvaptan administration.	Tolvaptan	24-33	aquaporin 2	Homo sapiens	196-200
26610908-9	2016	The degree of the decrease in urinary AQP2 levels and degree of the decrease in urinary osmolarity correlated significantly at 4 h (r = 0.452, P = 0.009) and 8 h (r = 0.384, P = 0.030) after tolvaptan administration.	Tolvaptan	191-200	aquaporin 2	Homo sapiens	38-42
26610908-10	2016	CONCLUSIONS: These results indicate that the vasopressin-AQP2 system plays a major role in fluid retention in cirrhosis and that the pharmacological effect of tolvaptan to inhibit water reabsorption can be monitored by measurement of the dynamics of urinary AQP2 levels.	Tolvaptan	159-168	arginine vasopressin	Homo sapiens	45-56
26610908-10	2016	CONCLUSIONS: These results indicate that the vasopressin-AQP2 system plays a major role in fluid retention in cirrhosis and that the pharmacological effect of tolvaptan to inhibit water reabsorption can be monitored by measurement of the dynamics of urinary AQP2 levels.	Tolvaptan	159-168	aquaporin 2	Homo sapiens	57-61
26610908-10	2016	CONCLUSIONS: These results indicate that the vasopressin-AQP2 system plays a major role in fluid retention in cirrhosis and that the pharmacological effect of tolvaptan to inhibit water reabsorption can be monitored by measurement of the dynamics of urinary AQP2 levels.	Tolvaptan	159-168	aquaporin 2	Homo sapiens	258-262
27184496-1	2016	BACKGROUND: Tolvaptan is the only vasopressin V2 receptor antagonist licensed by the European Medicines Agency for the treatment of hyponatraemia (HN) secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH).	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	34-57
26912543-1	2016	BACKGROUND: and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	31-40	arginine vasopressin receptor 2	Homo sapiens	202-225
26912543-1	2016	BACKGROUND: and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of kidney growth and eGFR decline in autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	237-246	arginine vasopressin receptor 2	Homo sapiens	202-225
26123753-1	2016	AIM: Recently, the short-term efficacy of the vasopressin V2 receptor antagonist tolvaptan for the treatment of ascites in cirrhosis was reported.	Tolvaptan	81-90	arginine vasopressin receptor 2	Homo sapiens	46-69
26921537-0	2016	Aquaporin-2 is a potential biomarker for tolvaptan efficacy in decompensated heart failure complicated by diabetic nephrotic syndrome.	Tolvaptan	41-50	aquaporin 2	Homo sapiens	0-11
27013400-1	2016	Tolvaptan is a selective V2-receptor antagonist primarily metabolized by CYP3A.	Tolvaptan	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	73-78
27013400-6	2016	Cellular accumulation of tolvaptan (0.15-50 muM), DM-4103 and DM-4107 in SCHH was concentration dependent.	Tolvaptan	25-34	latexin	Homo sapiens	44-47
27013400-7	2016	Tolvaptan accumulation (15 muM) in SCHH was not altered markedly by 50 muM pioglitazone, verapamil or MK-571, or 10 muM elacridar.	Tolvaptan	0-9	latexin	Homo sapiens	27-30
27013400-9	2016	Co-incubation with increasing tolvaptan concentrations (0.15-50 muM) decreased TCA (2.5 muM) cell+bile accumulation and the TCA biliary excretion index (BEI; from 76% to 51%), consistent with inhibition of the bile salt export pump (BSEP).	Tolvaptan	30-39	latexin	Homo sapiens	64-67
27013400-9	2016	Co-incubation with increasing tolvaptan concentrations (0.15-50 muM) decreased TCA (2.5 muM) cell+bile accumulation and the TCA biliary excretion index (BEI; from 76% to 51%), consistent with inhibition of the bile salt export pump (BSEP).	Tolvaptan	30-39	latexin	Homo sapiens	88-91
27013400-11	2016	Digoxin cellular accumulation increased and the BEI of digoxin decreased from 23.9% to 8.1% in the presence of 15 muM tolvaptan, consistent with inhibition of P-glycoprotein (P-gp).	Tolvaptan	118-127	latexin	Homo sapiens	114-117
27013400-11	2016	Digoxin cellular accumulation increased and the BEI of digoxin decreased from 23.9% to 8.1% in the presence of 15 muM tolvaptan, consistent with inhibition of P-glycoprotein (P-gp).	Tolvaptan	118-127	ATP binding cassette subfamily B member 1	Homo sapiens	159-173
27013400-11	2016	Digoxin cellular accumulation increased and the BEI of digoxin decreased from 23.9% to 8.1% in the presence of 15 muM tolvaptan, consistent with inhibition of P-glycoprotein (P-gp).	Tolvaptan	118-127	ATP binding cassette subfamily B member 1	Homo sapiens	175-179
26385871-7	2016	The mean sNa increase 24 h after tolvaptan initiation was 9 +- 3 9 mmol/l.	Tolvaptan	33-42	snail family transcriptional repressor 1	Homo sapiens	9-12
26385871-9	2016	At the end of tolvaptan therapy, sNa increase was 13 5 +- 5 9 mmol/l with 96 7% of patients having sNa increase >=5 mmol/l in 48 h. There was a negative significant correlation (P = 0 012) between baseline sNa and 24-h change; for every 1 mmol/l reduction in baseline value, sNa increased by an additional 0 23 mmol/l (95% CI 0 05-0 41).	Tolvaptan	14-23	snail family transcriptional repressor 1	Homo sapiens	33-36
26385871-9	2016	At the end of tolvaptan therapy, sNa increase was 13 5 +- 5 9 mmol/l with 96 7% of patients having sNa increase >=5 mmol/l in 48 h. There was a negative significant correlation (P = 0 012) between baseline sNa and 24-h change; for every 1 mmol/l reduction in baseline value, sNa increased by an additional 0 23 mmol/l (95% CI 0 05-0 41).	Tolvaptan	14-23	snail family transcriptional repressor 1	Homo sapiens	99-102
26385871-9	2016	At the end of tolvaptan therapy, sNa increase was 13 5 +- 5 9 mmol/l with 96 7% of patients having sNa increase >=5 mmol/l in 48 h. There was a negative significant correlation (P = 0 012) between baseline sNa and 24-h change; for every 1 mmol/l reduction in baseline value, sNa increased by an additional 0 23 mmol/l (95% CI 0 05-0 41).	Tolvaptan	14-23	snail family transcriptional repressor 1	Homo sapiens	99-102
26385871-9	2016	At the end of tolvaptan therapy, sNa increase was 13 5 +- 5 9 mmol/l with 96 7% of patients having sNa increase >=5 mmol/l in 48 h. There was a negative significant correlation (P = 0 012) between baseline sNa and 24-h change; for every 1 mmol/l reduction in baseline value, sNa increased by an additional 0 23 mmol/l (95% CI 0 05-0 41).	Tolvaptan	14-23	snail family transcriptional repressor 1	Homo sapiens	99-102
27022218-0	2016	Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites.	Tolvaptan	0-9	aquaporin 2	Rattus norvegicus	20-31
27022218-7	2016	CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group.	Tolvaptan	78-87	arginine vasopressin	Rattus norvegicus	35-46
27022218-9	2016	After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups.	Tolvaptan	24-33	aquaporin 2	Rattus norvegicus	35-40
26908832-1	2016	Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease.	Tolvaptan	99-108	arginine vasopressin receptor 2	Homo sapiens	64-87
26742474-3	2016	Survival rate and longitudinal models were used to estimate temporal changes in postdischarge all-cause mortality risk in 3,993 HHF patients discharged alive in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.	Tolvaptan	236-245	arginine vasopressin	Homo sapiens	177-188
26660633-7	2016	The half inhibitory concentration of tolvaptan on cell growth in HEK293/SULT1C3 cells and HEK293/CYP3A4 & SULT1C3 cells was significantly lower than that in the corresponding HEK293/vector cells or HEK293/CYP3A4 & SULT vector cells.	Tolvaptan	37-46	sulfotransferase family 1C member 3	Homo sapiens	72-79
26660633-7	2016	The half inhibitory concentration of tolvaptan on cell growth in HEK293/SULT1C3 cells and HEK293/CYP3A4 & SULT1C3 cells was significantly lower than that in the corresponding HEK293/vector cells or HEK293/CYP3A4 & SULT vector cells.	Tolvaptan	37-46	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	97-103
26660633-7	2016	The half inhibitory concentration of tolvaptan on cell growth in HEK293/SULT1C3 cells and HEK293/CYP3A4 & SULT1C3 cells was significantly lower than that in the corresponding HEK293/vector cells or HEK293/CYP3A4 & SULT vector cells.	Tolvaptan	37-46	sulfotransferase family 1C member 3	Homo sapiens	110-117
26660633-7	2016	The half inhibitory concentration of tolvaptan on cell growth in HEK293/SULT1C3 cells and HEK293/CYP3A4 & SULT1C3 cells was significantly lower than that in the corresponding HEK293/vector cells or HEK293/CYP3A4 & SULT vector cells.	Tolvaptan	37-46	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	209-215
26660633-8	2016	Moreover, exposing cells to tolvaptan in the presence of cyclosporine A, an inhibitor of the drug efflux transporters, significantly increased the intracellular levels of tolvaptan sulfate and decreased the cell viability in HEK293/SULT1C3 cells.	Tolvaptan	28-37	sulfotransferase family 1C member 3	Homo sapiens	232-239
26784173-0	2016	Urine Aquaporin-2: A Promising Marker of Response to the Arginine Vasopressin Type-2 Antagonist, Tolvaptan in Patients with Congestive Heart Failure.	Tolvaptan	97-106	aquaporin 2	Homo sapiens	6-17
26710331-2	2016	BACKGROUND: Tolvaptan, a vasopressin V2-receptor antagonist, has been reported to improve congestion in adult patients with heart failure.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	25-48
26072263-1	2016	BACKGROUND: Recent clinical trials have demonstrated the efficacy of short-term treatment with tolvaptan, an oral vasopressin V2 receptor antagonist, in patients with heart failure.	Tolvaptan	95-104	arginine vasopressin receptor 2	Homo sapiens	114-137
26784173-0	2016	Urine Aquaporin-2: A Promising Marker of Response to the Arginine Vasopressin Type-2 Antagonist, Tolvaptan in Patients with Congestive Heart Failure.	Tolvaptan	97-106	arginine vasopressin	Homo sapiens	66-77
26784173-2	2016	The arginine vasopressin type-2 antagonist, tolvaptan, is a new-generation diuretic; it is especially indicated in patients with decompensated heart failure refractory to conventional diuretics.	Tolvaptan	44-53	arginine vasopressin	Homo sapiens	13-24
26784173-4	2016	Urine aquaporin-2 has recently been demonstrated as a promising predictor of response to tolvaptan.	Tolvaptan	89-98	aquaporin 2	Homo sapiens	6-17
26784173-5	2016	We here validated aquaporin-2-guided tolvaptan therapy in patients with decompensated heart failure.	Tolvaptan	37-46	aquaporin 2	Homo sapiens	18-29
26784173-6	2016	Long-term efficacy of tolvaptan treatment in the responders defined by aquaporin-2 needs to be validated in the future prospective study.	Tolvaptan	22-31	aquaporin 2	Homo sapiens	71-82
27512786-7	2015	Tolvaptan, a selective arginine vasopressin V2 receptor antagonist, can be used to reduce the speed of disease progression in selected patients.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	32-55
27857840-4	2016	Tolvaptan is an oral, highly selective arginine vasopressin V2-receptor antagonist, which has been licensed in adults for the management of SIADH and has been used in treating paediatric heart failure.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	48-71
26742881-0	2016	Tolvaptan Prolongs Blockage of the Vasopressin Type II Receptor Over 24 Hours in Responders With Stage D Heart Failure.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	35-46
26742881-1	2016	The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV).	Tolvaptan	190-199	aquaporin 2	Homo sapiens	10-21
26742881-1	2016	The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV).	Tolvaptan	190-199	aquaporin 2	Homo sapiens	25-29
26742881-1	2016	The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV).	Tolvaptan	190-199	arginine vasopressin receptor 2	Homo sapiens	145-177
26742881-1	2016	The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV).	Tolvaptan	201-204	aquaporin 2	Homo sapiens	10-21
26742881-1	2016	The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV).	Tolvaptan	201-204	aquaporin 2	Homo sapiens	25-29
26742881-1	2016	The urine aquaporin-2 (U-AQP2) level relative to the plasma arginine vasopressin (P-AVP) level is a novel predictor of the responsiveness to the vasopressin type 2 receptor (V2R) antagonist tolvaptan (TLV).	Tolvaptan	201-204	arginine vasopressin receptor 2	Homo sapiens	145-177
26742881-5	2016	The U-AQP2 of the TLV-responders, corrected for the urine creatinine concentration, decreased significantly at 4 hours after TLV administration without returning to the day-1 morning level on the morning of day-7.	Tolvaptan	18-21	aquaporin 2	Homo sapiens	6-10
26742881-6	2016	The TLV-non-responder U-AQP2 levels remained low even before the TLV treatment.	Tolvaptan	4-7	aquaporin 2	Homo sapiens	24-28
26742881-7	2016	On the morning of day-7, the TLV-responder U-AQP2/P-AVP ratio was comparable to that of the TLV-non-responders.	Tolvaptan	29-32	aquaporin 2	Homo sapiens	45-49
27746425-2	2016	The aim of the study was to examine the effect of tolvaptan, a vasopressin V2 receptor antagonist, on the prognosis of cirrhosis.	Tolvaptan	50-59	arginine vasopressin receptor 2	Homo sapiens	63-86
26411431-1	2015	PURPOSE: The purpose of this study was to assess the efficacy of tolvaptan, a vasopressin V2 receptor antagonist, for the management of postoperative surgical fluid retention after heart valve surgery.	Tolvaptan	65-74	arginine vasopressin receptor 2	Homo sapiens	78-101
26385871-11	2016	Without rigorous electrolyte monitoring, tolvaptan carries a significant risk of overly rapid sodium correction, especially in patients with starting sNa <125 mmol/l.	Tolvaptan	41-50	snail family transcriptional repressor 1	Homo sapiens	150-153
27515480-8	2016	CONCLUSIONS: Plasma TLV concentrations correlated with the urine volume in late phase of treatment but not in early phase, which suggests that the effect of TLV may possibly be inhibited by renin-angiotensin-aldosterone system activity.	Tolvaptan	20-23	renin	Homo sapiens	190-195
27515480-8	2016	CONCLUSIONS: Plasma TLV concentrations correlated with the urine volume in late phase of treatment but not in early phase, which suggests that the effect of TLV may possibly be inhibited by renin-angiotensin-aldosterone system activity.	Tolvaptan	157-160	renin	Homo sapiens	190-195
26973271-0	2016	Combination of Urinary Sodium/Creatinine Ratio and Plasma Brain Natriuretic Peptide Level Predicts Successful Tolvaptan Therapy in Patients With Heart Failure and Volume Overload.	Tolvaptan	110-119	natriuretic peptide B	Homo sapiens	58-83
26973271-7	2016	Double-positive results of UNa/UCr < 46.5 mEq/g Cr and plasma BNP level > 778 pg/mL predicted unsuccessful tolvaptan therapy with high diagnostic accuracy (sensitivity 54%, specificity 100%, positive predictive value 100%, negative predictive value 89%, and accuracy 90%).	Tolvaptan	113-122	natriuretic peptide B	Homo sapiens	65-68
26885186-0	2015	Arginine vasopressin antagonist tolvaptan in the treatment of heart failure: a meta-analysis of randomized controlled trials.	Tolvaptan	32-41	arginine vasopressin	Homo sapiens	9-20
25429910-1	2015	AIM: Tolvaptan, an oral arginine vasopressin V2 receptor antagonist, became available for hepatic ascites.	Tolvaptan	5-14	arginine vasopressin receptor 2	Homo sapiens	33-56
26319417-5	2015	Application of AVP significantly stimulated the 80-150pS K(+) channel in the TAL and this effect was blocked by tolvaptan (V2 receptor antagonist) or by inhibiting PKA.	Tolvaptan	112-121	arginine vasopressin	Mus musculus	15-18
26516441-12	2015	We recommend selective oral administration of vasopressin V2-receptor antagonist, tolvaptan, which acts to increase the excretion of free water, thereby resolving hypervolemic hyponatremia and may have the potential to improve outcomes in these patients.	Tolvaptan	82-91	arginine vasopressin receptor 2	Homo sapiens	46-69
26109089-7	2015	Moreover, AQP2 upregulation and cAMP accumulation in response to 4-HC were significantly reduced by tolvaptan cotreatment in primary cultured IMCD cells and IMCD suspensions, respectively.	Tolvaptan	100-109	aquaporin 2	Rattus norvegicus	10-14
25543187-2	2015	Recent reports have shown that tolvaptan, a vasopressin V2 receptor antagonist, has been effective in inhibiting renal cyst proliferation and enlargement in ADPKD patients, although no biomarker has identified to predict the effects of tolvaptan.	Tolvaptan	31-40	arginine vasopressin receptor 2	Homo sapiens	44-67
25663351-7	2015	The annual estimated glomerular filtration rate change was -3.83 mL/min/1.73 m(2) in the tolvaptan group and -5.05 mL in the placebo group for a treatment effect of +1.22 mL/min/1.73 m(2) (95 % CI 0.41-2.02: P = 0.003).	Tolvaptan	89-98	CD59 molecule (CD59 blood group)	Homo sapiens	68-73
26407729-1	2015	Tolvaptan (Jinarc( )) is a highly selective vasopressin V2 receptor antagonist indicated for use in patients with autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	44-67
25689936-0	2015	Can serum albumin level affect the pharmacological action of tolvaptan in patients with liver cirrhosis?	Tolvaptan	61-70	albumin	Homo sapiens	10-17
26374918-7	2015	A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients.	Tolvaptan	67-76	arginine vasopressin	Homo sapiens	33-44
25997504-2	2015	Coadministration of tolvaptan, a selective vasopressin V2 receptor antagonist, can ameliorate such adverse events by reducing the required dose of loop diuretics; however, the safety of tolvaptan in patients with reduced renal function is not known.	Tolvaptan	20-29	arginine vasopressin receptor 2	Homo sapiens	43-66
26126090-1	2015	The vasopressin inhibitor tolvaptan is clinically effective in slowing growth of renal cysts and reduction in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD), but these effects are mitigated by the associated polyuria.	Tolvaptan	26-35	arginine vasopressin	Homo sapiens	4-15
26405324-3	2015	The use of tolvaptan, a vasopressin antagonist, outside of clinical trials has not been well characterized.	Tolvaptan	11-20	arginine vasopressin	Homo sapiens	24-35
25858412-6	2015	Exposure of HepG2 cells to tolvaptan enhanced cytochrome C release and triggered apoptosis by modulating Bcl-2 family members.	Tolvaptan	27-36	cytochrome c, somatic	Homo sapiens	46-58
25858412-6	2015	Exposure of HepG2 cells to tolvaptan enhanced cytochrome C release and triggered apoptosis by modulating Bcl-2 family members.	Tolvaptan	27-36	BCL2 apoptosis regulator	Homo sapiens	105-110
25858412-7	2015	The activation of p38 contributed to tolvaptan-mediated apoptosis via down-regulation of Bcl-2.	Tolvaptan	37-46	mitogen-activated protein kinase 14	Homo sapiens	18-21
25858412-7	2015	The activation of p38 contributed to tolvaptan-mediated apoptosis via down-regulation of Bcl-2.	Tolvaptan	37-46	BCL2 apoptosis regulator	Homo sapiens	89-94
25600953-1	2015	BACKGROUND: A recent study showed that tolvaptan, a vasopressin V2 receptor antagonist, decreased total kidney volume (TKV) growth and estimated glomerular filtration rate (GFR) loss in autosomal dominant polycystic kidney disease (ADPKD) with creatinine clearance>=60mL/min.	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	52-75
25728846-3	2015	A post hoc analysis was performed in 1,907 hospitalized patients with worsening HF and reduced EF in the placebo arm of the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan (EVEREST) trial.	Tolvaptan	184-193	arginine vasopressin	Homo sapiens	136-147
26148383-1	2015	BACKGROUND: Tolvaptan selectively binds to the vasopressin V2 receptor and inhibits reabsorption of free water.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	47-70
26714385-0	2015	The Vasopressin 2 Receptor Antagonist Tolvaptan Improves Nutrition and Inflammatory States in Peritoneal Dialysis Patients with Diabetes Mellitus.	Tolvaptan	38-47	arginine vasopressin	Homo sapiens	4-15
25734677-8	2015	Tolvaptan is a selective, oral vasopressin-V2-receptor-antagonist that inhibits ADH-induced retention of electrolyte-free water in the connecting duct of the kidney.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	31-54
25740389-3	2015	In this study (SMILE study), we administered tolvaptan to patients aged >= 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < 80 years (U-80).	Tolvaptan	45-54	transmembrane O-mannosyltransferase targeting cadherins 3	Homo sapiens	15-20
25740399-0	2015	Vasopressin V2 receptor antagonist tolvaptan is effective in heart failure patients with reduced left ventricular systolic function and low blood pressure.	Tolvaptan	35-44	arginine vasopressin receptor 2	Homo sapiens	0-23
25926290-1	2015	BACKGROUND/AIMS: Tolvaptan, a vasopressin V2 receptor antagonist, promotes the excretion of electrolyte-free water.	Tolvaptan	17-26	arginine vasopressin receptor 2	Homo sapiens	30-53
24988986-1	2014	Tolvaptan is a competitive vasopressin V2-receptor antagonist that inhibits water reabsorption in the renal collecting ducts.	Tolvaptan	0-9	arginine vasopressin receptor 2	Rattus norvegicus	27-50
24994926-0	2015	Tolvaptan plus pasireotide shows enhanced efficacy in a PKD1 model.	Tolvaptan	0-9	polycystin 1, transient receptor potential channel interacting	Homo sapiens	56-60
24994926-3	2015	Compounds such as tolvaptan and pasireotide, which indirectly reduce adenylyl cyclase 6 (AC6) activity, have hence proven effective in slowing cyst progression.	Tolvaptan	18-27	adenylate cyclase 6	Homo sapiens	69-87
24994926-3	2015	Compounds such as tolvaptan and pasireotide, which indirectly reduce adenylyl cyclase 6 (AC6) activity, have hence proven effective in slowing cyst progression.	Tolvaptan	18-27	adenylate cyclase 6	Homo sapiens	89-92
25179972-1	2014	The vasopressin V2 receptor antagonist (Tolvaptan) is a new diuretic that selectively promotes the excretion of water.	Tolvaptan	40-49	arginine vasopressin receptor 2	Homo sapiens	4-27
26237603-1	2014	Tolvaptan is an arginine vasopressin (AVP) antagonist that acts to increase excretion of free water (aquaresis) in patients without introducing electrolyte abnormalities or worsening renal function.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	25-36
25268207-7	2014	CONCLUSION: If restriction of fluid intake is not tolerated by the patients the vasopressin antagonist tolvaptan provides an alternative symptomatic treatment of paraneoplastic SIADH.	Tolvaptan	103-112	arginine vasopressin	Homo sapiens	80-91
25016163-1	2014	Tolvaptan is a competitive vasopressin V2-receptor antagonist that inhibits water reabsorption in the renal collecting ducts.	Tolvaptan	0-9	arginine vasopressin receptor 2	Rattus norvegicus	27-50
24678622-2	2014	In 2013, tolvaptan (7.5 mg/day), an arginine vasopressin V2 receptor antagonist, was approved in Japan for the treatment of liver cirrhosis with oedema.	Tolvaptan	9-18	arginine vasopressin receptor 2	Homo sapiens	45-68
24240509-3	2014	CASE-DIAGNOSIS/TREATMENT: We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.	Tolvaptan	169-178	arginine vasopressin receptor 2	Homo sapiens	197-220
24965902-1	2014	BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist (V2R) that increases free water excretion.	Tolvaptan	12-21	arginine vasopressin	Homo sapiens	37-48
24965902-9	2014	U-AQP2 decreased during both treatments, whereas u-ENaCgamma decreased after placebo and increased after tolvaptan.	Tolvaptan	105-114	sodium channel epithelial 1 subunit gamma	Homo sapiens	51-60
24673552-4	2014	The results with the mTOR inhibitors were disappointing, but more encouraging with the somatostatin analogues and with tolvaptan.	Tolvaptan	119-128	mechanistic target of rapamycin kinase	Homo sapiens	21-25
24706579-4	2014	Tolvaptan is an orally active, selective arginine vasopressin V2 receptor antagonist already in use for hyponatremia.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	50-73
24706579-6	2014	Metabolism occurs through the cytochrome P450 3A4 isoenzyme, and tolvaptan is a substrate for P-glycoprotein, resulting in numerous drug interactions.	Tolvaptan	65-74	ATP binding cassette subfamily B member 1	Homo sapiens	94-108
24570071-1	2014	Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	23-46
24570071-6	2014	Interestingly, tolvaptan also dose-dependently reduced urinary neutrophil gelatinase-associated lipocalin levels in correlation with the kidney volume.	Tolvaptan	15-24	lipocalin 2	Homo sapiens	63-105
30534332-2	2014	Tolvaptan, a vasopressin V2-receptor antagonist, has been reported to be effective in treating HF due to its potent effects of water diuresis and is expected to improve fluid retention without adversely affecting renal function.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	13-36
24048380-1	2014	The selective vasopressin V2-receptor antagonist tolvaptan is eliminated almost exclusively by non-renal mechanisms.	Tolvaptan	49-58	arginine vasopressin receptor 2	Homo sapiens	14-37
24048380-4	2014	Mean tolvaptan exposure was 90% higher in the under 30-ml/min group compared with the over 60-ml/min group with individual values significantly but negatively correlated with increasing baseline CrCL.	Tolvaptan	5-14	CRCL	Homo sapiens	195-199
24511399-5	2014	Vasopressin antagonists like tolvaptan seem promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure.	Tolvaptan	29-38	arginine vasopressin	Homo sapiens	0-11
24305472-10	2014	Specifically, tolvaptan almost completely inhibited the ability of vasopressin to increase AQP2 phosphorylation at Ser256, Ser264, and Ser269, while strongly inhibiting a vasopressin-induced decrease in AQP2 phosphorylation at Ser261.	Tolvaptan	14-23	aquaporin 2	Rattus norvegicus	203-207
24743526-1	2014	We report clinical effects of tolvaptan, a vasopressin V2 receptor antagonist, in cardiac surgery.	Tolvaptan	30-39	arginine vasopressin receptor 2	Homo sapiens	43-66
24305472-5	2014	We designed an in vivo protocol to investigate vasopressin responses in the rat kidney using osmotic minipumps loaded with tolvaptan, a nonpeptide competitive inhibitor of the vasopressin V2 receptor.	Tolvaptan	123-132	arginine vasopressin	Rattus norvegicus	47-58
24305472-5	2014	We designed an in vivo protocol to investigate vasopressin responses in the rat kidney using osmotic minipumps loaded with tolvaptan, a nonpeptide competitive inhibitor of the vasopressin V2 receptor.	Tolvaptan	123-132	arginine vasopressin receptor 2	Rattus norvegicus	176-199
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	aquaporin 2	Rattus norvegicus	74-85
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	aquaporin 2	Rattus norvegicus	87-91
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	aquaporin 3 (Gill blood group)	Rattus norvegicus	94-105
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	aquaporin 3 (Gill blood group)	Rattus norvegicus	107-111
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	sodium channel epithelial 1 subunit beta	Rattus norvegicus	165-174
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	sodium channel epithelial 1 subunit gamma	Rattus norvegicus	181-191
24305472-7	2014	The tolvaptan infusion produced large decreases in the renal abundance of aquaporin-2 (AQP2), aquaporin-3 (AQP3), the beta-subunit of the epithelial sodium channel (beta-ENaC), and gamma-ENaC that were comparable to the differences seen in vehicle-infused vs. vasopressin-infused Brattleboro rats.	Tolvaptan	4-13	arginine vasopressin	Rattus norvegicus	260-271
24305472-8	2014	Thus we conclude that tolvaptan infusion in rats provides an additional model (besides dDAVP-infusion in the Brattleboro rat) for the assessment of V2 receptor-mediated vasopressin actions in the kidney.	Tolvaptan	22-31	arginine vasopressin	Rattus norvegicus	169-180
24305472-9	2014	We also provide ancillary in vitro data in rat inner-medullary-collecting-duct suspensions showing that tolvaptan can block vasopressin"s effects on phosphorylation of the water channel AQP2 in vitro.	Tolvaptan	104-113	arginine vasopressin	Rattus norvegicus	124-135
24305472-9	2014	We also provide ancillary in vitro data in rat inner-medullary-collecting-duct suspensions showing that tolvaptan can block vasopressin"s effects on phosphorylation of the water channel AQP2 in vitro.	Tolvaptan	104-113	aquaporin 2	Rattus norvegicus	186-190
24305472-10	2014	Specifically, tolvaptan almost completely inhibited the ability of vasopressin to increase AQP2 phosphorylation at Ser256, Ser264, and Ser269, while strongly inhibiting a vasopressin-induced decrease in AQP2 phosphorylation at Ser261.	Tolvaptan	14-23	arginine vasopressin	Rattus norvegicus	67-78
24305472-10	2014	Specifically, tolvaptan almost completely inhibited the ability of vasopressin to increase AQP2 phosphorylation at Ser256, Ser264, and Ser269, while strongly inhibiting a vasopressin-induced decrease in AQP2 phosphorylation at Ser261.	Tolvaptan	14-23	aquaporin 2	Rattus norvegicus	91-95
24305472-10	2014	Specifically, tolvaptan almost completely inhibited the ability of vasopressin to increase AQP2 phosphorylation at Ser256, Ser264, and Ser269, while strongly inhibiting a vasopressin-induced decrease in AQP2 phosphorylation at Ser261.	Tolvaptan	14-23	arginine vasopressin	Rattus norvegicus	171-182
24954239-0	2014	Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure.	Tolvaptan	101-110	aquaporin 2	Homo sapiens	16-27
25383228-1	2014	Dilutional hyponatremia is common in decompensated cirrhosis and can be successfully treated by tolvaptan, a vasopressin V2-receptor antagonist.	Tolvaptan	96-105	arginine vasopressin receptor 2	Homo sapiens	109-132
24954239-0	2014	Increased urine aquaporin-2 relative to plasma arginine vasopressin is a novel marker of response to tolvaptan in patients with decompensated heart failure.	Tolvaptan	101-110	arginine vasopressin	Homo sapiens	56-67
24954239-1	2014	BACKGROUND: Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.	Tolvaptan	132-141	arginine vasopressin receptor 2	Homo sapiens	97-119
24954239-1	2014	BACKGROUND: Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.	Tolvaptan	143-146	arginine vasopressin receptor 2	Homo sapiens	97-119
24954239-10	2014	CONCLUSIONS: U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF.	Tolvaptan	62-65	aquaporin 2	Homo sapiens	15-19
25008484-2	2014	Clinical data establishing the efficacy and safety of tolvaptan, a selective oral vasopressin V2 receptor antagonist that induces aquaresis, have recently been accumulated over 3 years of daily clinical experience in Japan.	Tolvaptan	54-63	arginine vasopressin receptor 2	Homo sapiens	82-105
24671837-7	2014	In Europe, the oral tolvaptan has been commercialized only for the treatment of euvolemic hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone).Conversely in the USA, intravenous conivaptan (V1a/V2 vasopressin receptor antagonist) and oral tolvaptan have been marketed for the treatment of both euvolemic and hypervolemic hyponatremia.Besides being effective drugs, aquaretics have the benefit of having drawn the attention of physicians against hyponatremia.	Tolvaptan	20-29	arginine vasopressin receptor 1A	Homo sapiens	225-252
23551935-10	2014	Even in patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163).	Tolvaptan	96-105	albumin	Homo sapiens	32-39
24095030-3	2013	In this retrospective analysis of the placebo group of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial, we evaluated 1,982 patients hospitalized for worsening HF with ejection fractions <=40%.	Tolvaptan	130-139	arginine vasopressin	Homo sapiens	71-82
24949180-3	2014	In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function.	Tolvaptan	53-62	arginine vasopressin	Homo sapiens	30-41
25318553-5	2014	The expression of aquaporin-2 in the collecting duct, which is related to the action of tolvaptan, was investigated by immunohistochemistry using the kidney tissue obtained for the diagnosis.Responses were seen in 19 of the patients.	Tolvaptan	88-97	aquaporin 2	Homo sapiens	18-29
25318553-10	2014	There are no clear parameters for predicting an effect, but the present study showed that aquaporin-2 was expressed in the epithelial cells of the collecting ducts of tolvaptan responders.	Tolvaptan	167-176	aquaporin 2	Homo sapiens	90-101
25318555-0	2014	Aquaporin-2-guided tolvaptan therapy in patients with congestive heart failure accompanied by chronic kidney disease.	Tolvaptan	19-28	aquaporin 2	Homo sapiens	0-11
23858000-4	2013	METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial was an event-driven, randomized, double-blind, placebo-controlled study of tolvaptan in 4133 patients hospitalized for worsening HF with an EF <40%.	Tolvaptan	96-105	arginine vasopressin	Homo sapiens	37-48
24142853-4	2013	The purpose of this study was to examine the efficacy and safety of tolvaptan, which is a selective vasopressin V2 receptor antagonist and produces water excretion without changes in sodium excretion, compared with carperitide.	Tolvaptan	68-77	arginine vasopressin receptor 2	Homo sapiens	100-123
23413814-0	2013	Tolvaptan, an orally active non-peptide arginine vasopressin V2 receptor antagonist, reduces ascites in rats with chronic liver injury.	Tolvaptan	0-9	arginine vasopressin receptor 2	Rattus norvegicus	49-72
23206923-3	2013	In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), 3,957 patients hospitalized for worsening HF with ejection fractions <=40% were examined.	Tolvaptan	104-113	arginine vasopressin	Homo sapiens	45-56
30546768-1	2013	Tolvaptan (TLV), which is an antagonist to the vasopressin V2 receptor, was approved by Japanese authorities for the treatment of "volume overload in heart failure when adequate response is not obtained with other diuretics (e.g. loop diuretics)".	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	47-70
30546768-1	2013	Tolvaptan (TLV), which is an antagonist to the vasopressin V2 receptor, was approved by Japanese authorities for the treatment of "volume overload in heart failure when adequate response is not obtained with other diuretics (e.g. loop diuretics)".	Tolvaptan	11-14	arginine vasopressin receptor 2	Homo sapiens	47-70
23483323-1	2013	BACKGROUND: Tolvaptan, a diuretic with a new mechanism of action, selectively binds to the vasopressin V2 receptor and inhibits reabsorption of water.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	91-114
23736843-7	2013	A phase III clinical trial investigating the effect of the V2R antagonist tolvaptan in ADPKD patients has shown that this treatment blunts kidney growth, reduces associated symptoms and slows kidney function decline when given over 3 years.	Tolvaptan	74-83	arginine vasopressin receptor 2	Homo sapiens	59-62
23743487-0	2013	Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan.	Tolvaptan	142-151	arginine vasopressin	Homo sapiens	105-116
23743487-3	2013	METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan database was examined to assess the short-term clinical course of patients hospitalized with heart failure and hyponatremia and the effect of tolvaptan on outcomes.	Tolvaptan	96-105	arginine vasopressin	Homo sapiens	37-48
22884529-0	2013	Hyponatremia in critical care patients: frequency, outcome, characteristics, and treatment with the vasopressin V2-receptor antagonist tolvaptan.	Tolvaptan	135-144	arginine vasopressin receptor 2	Homo sapiens	100-123
22884529-5	2013	The oral selective vasopressin V2-receptor antagonist tolvaptan is effective in treating euvolemic and hypervolemic hyponatremia and may be useful in the management of hyponatremic critical care patients.	Tolvaptan	54-63	arginine vasopressin receptor 2	Homo sapiens	19-42
23371016-0	2013	Letter in response to the recently published review: hyponatremia in cirrhosis and end-stage liver disease--treatment with the vasopressin v2-receptor antagonist tolvaptan.	Tolvaptan	162-171	arginine vasopressin receptor 2	Homo sapiens	127-150
23463968-2	2013	Tolvaptan is an orally active antagonist of arginine vasopressin type 2 receptors in the collecting duct of the kidney that inhibits water reabsorption without substantially affecting the electrolyte balance.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	53-64
23351825-0	2013	Clinical profile and prognostic value of low systolic blood pressure in patients hospitalized for heart failure with reduced ejection fraction: insights from the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial.	Tolvaptan	234-243	arginine vasopressin	Homo sapiens	174-185
23059198-3	2013	METHODS AND RESULTS: Post-hoc analysis was performed on the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) study, a randomized trial of patients hospitalized with HF (n = 4133) with median follow-up of 9.9 months.	Tolvaptan	140-149	arginine vasopressin	Homo sapiens	81-92
22999071-2	2012	We retrospectively analyzed the clinical characteristics and outcomes of patients according to gender in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.	Tolvaptan	180-189	arginine vasopressin	Homo sapiens	121-132
23297121-1	2013	Tolvaptan is an oral vasopressin V2-receptor antagonist recognized as effective for fluid retention associated with congestive heart failure and liver cirrhosis.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	21-44
23274625-1	2013	Tolvaptan is a selective vasopressin V(2)-receptor antagonist mainly used for the treatment of hyponatremia.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	25-50
23239836-3	2013	METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial investigated the effects of tolvaptan in patients with worsening heart failure and ejection fraction <=40%.	Tolvaptan	96-105	arginine vasopressin	Homo sapiens	37-48
23239836-10	2013	Tolvaptan therapy increased the proportion of patients with elevated AVP (P<0.001), but this had no effect on mortality (hazard ratio, 0.95; 95% confidence interval, 0.72-1.24).	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	69-72
23239836-12	2013	Tolvaptan treatment increased AVP levels during follow-up, but this incremental increase was not associated with worsened outcomes.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	30-33
23676370-0	2013	Renoprotective effect of vasopressin v2 receptor antagonist tolvaptan in Dahl rats with end-stage heart failure.	Tolvaptan	60-69	arginine vasopressin receptor 2	Rattus norvegicus	25-48
23676370-1	2013	Tolvaptan is a highly selective and orally effective arginine vasopressin V2 receptor antagonist, and is potentially useful for the treatment of heart failure (HF) patients.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	62-85
23676370-7	2013	Decreased expression of nephrin and podocin and increased desmin-positive area in failing rats were restored by tolvaptan.	Tolvaptan	112-121	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	24-31
23676370-7	2013	Decreased expression of nephrin and podocin and increased desmin-positive area in failing rats were restored by tolvaptan.	Tolvaptan	112-121	NPHS2 stomatin family member, podocin	Rattus norvegicus	36-43
23676370-9	2013	Tolvaptan administration resulted in significant inhibition of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression, and nuclear factor-kappaB phosphorylation.	Tolvaptan	0-9	tumor necrosis factor	Rattus norvegicus	63-90
23676370-9	2013	Tolvaptan administration resulted in significant inhibition of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression, and nuclear factor-kappaB phosphorylation.	Tolvaptan	0-9	C-C motif chemokine ligand 2	Rattus norvegicus	95-129
23676370-10	2013	We concluded that long-term tolvaptan therapy may improve renal dysfunction, glomerulosclerosis, podocyte injury, and inflammation associated with oxidative stress, as well as EMT, ERK, and the Rho-kinase pathway in the failing heart of DS rats.	Tolvaptan	28-37	Eph receptor B1	Rattus norvegicus	181-184
22984091-8	2012	Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-beta1, arginine vasopressin V(1a) receptor, and endothelin-1 in the marginal infarct region.	Tolvaptan	0-9	C-C motif chemokine ligand 2	Rattus norvegicus	95-159
22917555-2	2012	The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) examined the effects of tolvaptan in patients with worsening HF and EF <=40%.	Tolvaptan	75-84	arginine vasopressin	Homo sapiens	16-27
23068288-5	2012	Whereas plasma arginine-vasopressin levels, serum aldosterone concentration, and plasma renin activity mildly increased, plasma levels of B-type natriuretic peptide and atrial natriuretic peptide significantly decreased after tolvaptan treatment.	Tolvaptan	226-235	arginine vasopressin	Homo sapiens	24-35
22984091-8	2012	Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-beta1, arginine vasopressin V(1a) receptor, and endothelin-1 in the marginal infarct region.	Tolvaptan	0-9	arginine vasopressin receptor 1A	Rattus norvegicus	170-196
22984091-8	2012	Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-beta1, arginine vasopressin V(1a) receptor, and endothelin-1 in the marginal infarct region.	Tolvaptan	0-9	endothelin 1	Rattus norvegicus	202-214
23051949-3	2012	METHODS AND RESULTS: We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction <=40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 months.	Tolvaptan	132-141	arginine vasopressin	Homo sapiens	73-84
22971027-1	2012	Tolvaptan is a member of a new class of drugs, called the vaptans, that antagonize receptors of the neurohormone arginine vasopressin.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	122-133
22732834-0	2012	Hyponatremia in cirrhosis and end-stage liver disease: treatment with the vasopressin V2-receptor antagonist tolvaptan.	Tolvaptan	109-118	arginine vasopressin receptor 2	Homo sapiens	74-97
22732834-7	2012	Tolvaptan, a selective vasopressin V(2)-receptor antagonist, is the only oral agent in this class approved for raising sodium levels in hypervolemic and euvolemic hyponatremia.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	23-48
22130104-1	2012	Tolvaptan is a selective arginine vasopressin V2-receptor antagonist that is used as an aquaretic agent.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	34-57
22628529-1	2012	BACKGROUND: Although recent clinical trials have demonstrated the efficacy of the oral vasopressin (AVP) type 2 receptor (V2R) antagonist tolvaptan, its long-term effects on the myocardium and kidney in heart failure (HF) are not clear.	Tolvaptan	138-147	arginine vasopressin receptor 2	Rattus norvegicus	87-125
21607553-1	2012	Tolvaptan, an oral, selective arginine vasopressin (AVP) V2 receptor antagonist has been approved for the treatment of euvolemic and hypervolemic hyponatremia in the United States.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	52-55
21607553-6	2012	The mean increase in SNa of 6.4 mEq/L (range 2-10 mEq/L) 24 h post-tolvaptan was not different in the two groups of patients, but SIADH patients had higher pre and post-tolvaptan SNa levels than CHF patients.	Tolvaptan	67-76	snail family transcriptional repressor 1	Homo sapiens	21-24
22323742-2	2012	Tolvaptan decreases aquaporin expression in renal collecting ducts, by inhibiting antidiuretic hormone (ADH)-V2 receptors, to promote free water clearance.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	82-102
22487409-1	2012	New treatment methods of syndrome of inappropriate antidiuretic hormone secretion (SIADH) has emerged with the oral vasopressin V2-receptor antagonist (VV2RA) tolvaptan, but its therapeutic window remains to be defined.	Tolvaptan	159-168	arginine vasopressin receptor 2	Homo sapiens	116-139
22120092-3	2011	In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients.	Tolvaptan	55-64	arginine vasopressin receptor 2	Homo sapiens	80-103
22027579-0	2012	Tolvaptan, an oral vasopressin antagonist, in the treatment of hyponatremia in cirrhosis.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	19-30
22027579-1	2012	BACKGROUND & AIMS: Tolvaptan is a vasopressin V2-receptor antagonist that improves serum sodium concentration by increasing renal solute-free water excretion.	Tolvaptan	23-32	arginine vasopressin receptor 2	Homo sapiens	38-61
22111754-1	2012	BACKGROUND: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial showed that tolvaptan use improved heart failure (HF) signs and symptoms without serious adverse events.	Tolvaptan	87-96	arginine vasopressin	Homo sapiens	28-39
22111754-1	2012	BACKGROUND: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial showed that tolvaptan use improved heart failure (HF) signs and symptoms without serious adverse events.	Tolvaptan	125-134	arginine vasopressin	Homo sapiens	28-39
22722264-10	2012	The AVPR2 antagonists tolvaptan and satavaptan (prescribed before the diagnosis of NSIAD was made) showed no efficacy in 1 patient.	Tolvaptan	22-31	arginine vasopressin receptor 2	Homo sapiens	4-9
21816754-0	2011	Tolvaptan inhibits ERK-dependent cell proliferation, Cl- secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin.	Tolvaptan	0-9	mitogen-activated protein kinase 1	Homo sapiens	19-22
21816754-0	2011	Tolvaptan inhibits ERK-dependent cell proliferation, Cl- secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	128-139
21816754-5	2011	Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC(50) of ~10(-10) M. Correspondingly, tolvaptan inhibited AVP-induced ERK signaling and cell proliferation.	Tolvaptan	0-9	mitogen-activated protein kinase 1	Homo sapiens	173-176
22357577-3	2012	METHODS AND RESULTS: A post-hoc analysis was carried out of the placebo group of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) trial, which enrolled patients hospitalized for HF with an ejection fraction (EF) <=40% and no history of primary significant liver disease or acute hepatic failure.	Tolvaptan	165-174	arginine vasopressin	Homo sapiens	106-117
22437213-6	2012	The oral selective V(2)-receptor antagonist tolvaptan blocks arginine vasopressin effects in the renal collecting ducts, promoting aquaresis without increasing sodium/potassium excretion.	Tolvaptan	44-53	arginine vasopressin	Homo sapiens	70-81
22257581-1	2012	Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US) or cardiac edema (Japan).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	25-48
22103869-6	2011	One of these vaptans - tolvaptan - is an oral vasopressin V2-receptor antagonist that induces free water excretion without increasing sodium excretion.	Tolvaptan	23-32	arginine vasopressin receptor 2	Homo sapiens	46-69
21816754-5	2011	Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC(50) of ~10(-10) M. Correspondingly, tolvaptan inhibited AVP-induced ERK signaling and cell proliferation.	Tolvaptan	141-150	mitogen-activated protein kinase 1	Homo sapiens	173-176
22120093-3	2011	Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	42-65
22120094-1	2011	PURPOSE: This study aimed to investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of tolvaptan, an orally effective vasopressin V2-receptor antagonist.	Tolvaptan	104-113	arginine vasopressin receptor 2	Homo sapiens	135-158
22120095-1	2011	PURPOSE: We investigated the effects of tolvaptan, a vasopressin V(2)-receptor antagonist, on diuretic response and systemic and renal hemodynamic characteristics in conscious dogs with congestive heart failure (CHF).	Tolvaptan	40-49	arginine vasopressin receptor 2	Canis lupus familiaris	53-78
22120096-1	2011	PURPOSE: The aim of this study was to evaluate the therapeutic efficacy of tolvaptan, a vasopressin V(2) receptor antagonist, on edema in two rat models: 1) histamine-induced vascular hyperpermeability of the dorsal skin and 2) carrageenan-induced paw edema.	Tolvaptan	75-84	arginine vasopressin receptor 2	Rattus norvegicus	88-113
20679500-6	2011	In vitro studies in control and MDR1-expressing LLC-PK1 cells indicate that tolvaptan is a substrate of P-glycoprotein.	Tolvaptan	76-85	ATP-binding cassette, sub-family B (MDR/TAP), member 1	Sus scrofa	32-36
21641352-3	2011	This study explores the clinical effects of tolvaptan, a vasopressin-2-receptor antagonist, in addition to standard medical therapies on physician-assessed signs and symptoms in hospitalized AHFS patients.	Tolvaptan	44-53	arginine vasopressin	Homo sapiens	57-68
21317283-1	2011	OBJECTIVE: Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies.	Tolvaptan	11-20	arginine vasopressin receptor 2	Homo sapiens	48-73
21881396-7	2011	Tolvaptan is an orally active, selective V2-receptor antagonist that blocks the effects of arginine vasopressin in the renal collecting duct to promote aquaresis without increasing sodium or potassium excretion; as a result, it increases serum sodium in a controlled manner.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	100-111
20708094-3	2010	The purpose of this review is to update the current status of experimental and clinical studies with available vasopressin receptor antagonists (conivaptan and tolvaptan) and their potential role in the treatment of HF and hyponatremia of multiple causes.	Tolvaptan	160-169	arginine vasopressin	Homo sapiens	111-122
20868352-12	2011	Since tolvaptan is metabolized by the cytochrome CYP3A4 in the liver physicians should be aware of possible drug to drug interactions.	Tolvaptan	6-15	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	49-55
21694950-2	2011	Tolvaptan inhibits the binding of arginine vasopressin to the V(2) receptors on the collecting ducts of the kidneys resulting in aquaresis, the electrolytes sparing excretion of water.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	43-54
21104220-8	2010	Tolvaptan is a selective antagonist of the antidiuretic effect of vasopressin without primarily affecting blood pressure and depending on the dose leads to increased excretion of free water (aquaresis).	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	66-77
21192248-4	2011	Tolvaptan (TOL; selective V2 antagonist) and Conivaptan (CON; dual V1a/V2 antagonist) are two AVP antagonists that counteract the action of AVP with distinct profiles.	Tolvaptan	0-9	arginine vasopressin	Canis lupus familiaris	94-97
21192248-4	2011	Tolvaptan (TOL; selective V2 antagonist) and Conivaptan (CON; dual V1a/V2 antagonist) are two AVP antagonists that counteract the action of AVP with distinct profiles.	Tolvaptan	0-9	arginine vasopressin	Canis lupus familiaris	140-143
20926941-5	2010	Conivaptan is a nonselective AVP antagonist that is available intravenously, and tolvaptan is a V2 selective AVP antagonist that is available as an oral tablet.	Tolvaptan	81-90	arginine vasopressin	Homo sapiens	109-112
21180368-4	2010	Tolvaptan antagonises receptors for arginine vasopressin, a hormone that regulates blood sodium levels by stimulating renal water resabsorption.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	45-56
22111741-0	2010	Tolvaptan: a vasopressin antagonist for the management of euvolemic and hypervolemic hyponatremia.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	13-24
22111741-1	2010	Tolvaptan is a new vasopressin antagonist developed for the treatment of hypervolemic or euvolemic hyponatremia.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	19-30
20176717-3	2010	We hypothesized that combining BNP to the V(2)-receptor antagonist tolvaptan (TLV) would enhance renal excretory function by augmenting sodium excretion together with aquaresis without adversely affecting renal hemodynamics in experimental congestive heart failure.	Tolvaptan	78-81	natriuretic peptide B	Canis lupus familiaris	31-34
20608824-7	2010	Two nonpeptide vasopressin-receptor antagonists, conivaptan and tolvaptan, have recently been approved by American and European drug authorities for clinical use.	Tolvaptan	64-73	arginine vasopressin	Homo sapiens	15-26
20392812-3	2010	Tolvaptan, a vasopressin V(2) receptor antagonist, was used to correct hyponatremia and determine any potential benefits of such treatment in this condition.	Tolvaptan	0-9	arginine vasopressin receptor 2	Rattus norvegicus	13-38
20392812-7	2010	This reduced step-through latency was improved by the treatment of tolvaptan (0.25-8 mg/kg daily doses), a vasopressin V(2) receptor antagonist.	Tolvaptan	67-76	arginine vasopressin receptor 2	Rattus norvegicus	107-132
20637957-1	2010	BACKGROUND: Tolvaptan is an oral nonpeptide selective vasopressin V(2)-receptor antagonist indicated for the treatment of clinically relevant hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or syndrome of inappropriate antidiuretic hormone.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	54-79
20387081-1	2010	OBJECTIVES: We examined the efficacy of tolvaptan, an orally effective nonpeptide vasopressin V(2) receptor antagonist, in a Japanese clinical study in patients with intractable ascites and/or lower limb edema associated with decompensated liver cirrhosis.	Tolvaptan	40-49	arginine vasopressin receptor 2	Homo sapiens	82-107
20508668-0	2010	Hyponatremia: Prolonged use of the vasopressin antagonist tolvaptan is a safe and effective treatment for hyponatremia.	Tolvaptan	58-67	arginine vasopressin	Homo sapiens	35-46
20435194-0	2010	Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: results from Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) program.	Tolvaptan	224-233	arginine vasopressin	Homo sapiens	165-176
20435194-3	2010	METHODS: This was a prespecified analysis of adjudicated cause-specific all-cause mortality and cardiovascular (CV) hospitalization in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, a randomized, double-blind, placebo-controlled study in patients hospitalized with worsening HF and left ventricular ejection fraction < or =40% comparing tolvaptan, an oral vasopressin receptor antagonist to placebo, in addition to standard care.	Tolvaptan	210-219	arginine vasopressin	Homo sapiens	151-162
20435194-3	2010	METHODS: This was a prespecified analysis of adjudicated cause-specific all-cause mortality and cardiovascular (CV) hospitalization in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, a randomized, double-blind, placebo-controlled study in patients hospitalized with worsening HF and left ventricular ejection fraction < or =40% comparing tolvaptan, an oral vasopressin receptor antagonist to placebo, in addition to standard care.	Tolvaptan	395-404	arginine vasopressin	Homo sapiens	151-162
20197265-3	2010	METHODS AND RESULTS: In the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with tolvaptan, 1528 hospitalized patients (ejection fraction < or =40%) with a physical examination, laboratories, and health status [Kansas City Cardiomyopathy Questionnaire (KCCQ)] assessments 1 week after discharge were included.	Tolvaptan	99-108	arginine vasopressin	Homo sapiens	40-51
20205486-1	2010	Tolvaptan is an orally administered, nonpeptide, selective arginine vasopressin V(2) receptor antagonist that increases free water clearance, thereby correcting low serum sodium levels.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	68-93
20467590-4	2010	Tolvaptan is a new selective nonpeptide vasopressin V2 receptor antagonist that has shown to rapidly normalize serum sodium concentrations in hyponatremic patients.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	40-63
20467590-6	2010	Data from phase III studies including over 5,000 patients have demonstrated that tolvaptan is a safe and well tolerated vasopressin receptor antagonist, whose long-term use is not associated with adverse outcomes.	Tolvaptan	81-90	arginine vasopressin	Homo sapiens	120-131
19452240-0	2009	Tolvaptan, a selective oral vasopressin V2 receptor antagonist, ameliorates podocyte injury in puromycin aminonucleoside nephrotic rats.	Tolvaptan	0-9	arginine vasopressin receptor 2	Rattus norvegicus	28-51
19452240-9	2009	In tolvaptan-treated rats, nephrin and podocin expressions retained their normal linear pattern.	Tolvaptan	3-12	NPHS1 adhesion molecule, nephrin	Rattus norvegicus	27-34
19452240-9	2009	In tolvaptan-treated rats, nephrin and podocin expressions retained their normal linear pattern.	Tolvaptan	3-12	NPHS2 stomatin family member, podocin	Rattus norvegicus	39-46
19644472-1	2009	In May 2009, tolvaptan (Samsca; Otsuka), a selective vasopressin V(2) receptor antagonist, was approved by the US FDA for the treatment of clinically significant hypervolaemic and euvolaemic hyponatraemia.	Tolvaptan	13-22	arginine vasopressin receptor 2	Homo sapiens	53-78
19007589-0	2008	Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction: an international, multicenter, randomized, placebo-controlled trial.	Tolvaptan	29-38	arginine vasopressin receptor 2	Homo sapiens	42-65
19092365-7	2009	Tolvaptan, conivaptan, and lixivaptan are some of the vasopressin antagonists that have been studied in heart failure.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	54-65
19337422-8	2008	In addition, tolvaptan is metabolized by the CYP3A4 system; thus physicians should be aware of the potential for increased interactions with other medications.	Tolvaptan	13-22	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	45-51
18992654-10	2008	(Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan [EVEREST]; NCT00071331).	Tolvaptan	73-82	arginine vasopressin	Homo sapiens	13-24
19007589-2	2008	BACKGROUND: In decompensated heart failure (HF), tolvaptan, a vasopressin V(2) receptor antagonist, has been shown to improve congestion.	Tolvaptan	49-58	arginine vasopressin receptor 2	Homo sapiens	62-87
18544725-4	2008	DESIGN, SETTING, AND PARTICIPANTS: Retrospective, post hoc analysis from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study in patients hospitalized for heart failure and having an LVEF of 40% or less.	Tolvaptan	148-157	arginine vasopressin	Homo sapiens	89-100
18434616-4	2008	The arginine vasopressin V2 receptor antagonists OPC-31260 and tolvaptan inhibit the development of polycystic kidney disease in cpk mice and in three animal orthologs to human autosomal recessive polycystic kidney disease (PCK rat), autosomal dominant polycystic kidney disease (Pkd2-/WS25 mice), and nephronophthisis(pcy mouse).	Tolvaptan	63-72	arginine vasopressin receptor 2	Mus musculus	13-36
18434616-4	2008	The arginine vasopressin V2 receptor antagonists OPC-31260 and tolvaptan inhibit the development of polycystic kidney disease in cpk mice and in three animal orthologs to human autosomal recessive polycystic kidney disease (PCK rat), autosomal dominant polycystic kidney disease (Pkd2-/WS25 mice), and nephronophthisis(pcy mouse).	Tolvaptan	63-72	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	224-227
19018685-0	2008	EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan.	Tolvaptan	86-95	arginine vasopressin	Homo sapiens	27-38
19018685-7	2008	This paper provides an overview of a new compound, tolvaptan, an oral selective V(2)-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.	Tolvaptan	51-60	arginine vasopressin	Homo sapiens	85-96
19018685-7	2008	This paper provides an overview of a new compound, tolvaptan, an oral selective V(2)-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.	Tolvaptan	51-60	arginine vasopressin	Homo sapiens	155-166
20694082-2	2008	Tolvaptan is a vasopressin V(2) receptor antagonist that blocks the effect of arginine vasopressin (AVP) in reabsorbing water from the collecting ducts of the nephrons in congestive heart failure.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	15-40
20694082-2	2008	Tolvaptan is a vasopressin V(2) receptor antagonist that blocks the effect of arginine vasopressin (AVP) in reabsorbing water from the collecting ducts of the nephrons in congestive heart failure.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	15-26
18510477-5	2008	Tolvaptan, a vasopressin receptor antagonist, has been shown to improve diuresis and symptom relief without adversely affecting renal function, and may be a promising novel therapeutic agent in the growing population of patients with heart failure.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	13-24
18519091-4	2008	The arginine vasopressin V2 receptor antagonists OPC-31260 and tolvaptan inhibit the development of polycystic kidney disease in cpk mice and in three animal orthologs to human autosomal recessive polycystic kidney disease (PCK rat), autosomal dominant polycystic kidney disease (Pkd2/WS25 mice), and nephronophthisis (pcy mouse).	Tolvaptan	63-72	arginine vasopressin receptor 2	Mus musculus	13-36
18519091-4	2008	The arginine vasopressin V2 receptor antagonists OPC-31260 and tolvaptan inhibit the development of polycystic kidney disease in cpk mice and in three animal orthologs to human autosomal recessive polycystic kidney disease (PCK rat), autosomal dominant polycystic kidney disease (Pkd2/WS25 mice), and nephronophthisis (pcy mouse).	Tolvaptan	63-72	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	224-227
18519091-4	2008	The arginine vasopressin V2 receptor antagonists OPC-31260 and tolvaptan inhibit the development of polycystic kidney disease in cpk mice and in three animal orthologs to human autosomal recessive polycystic kidney disease (PCK rat), autosomal dominant polycystic kidney disease (Pkd2/WS25 mice), and nephronophthisis (pcy mouse).	Tolvaptan	63-72	polycystin 2, transient receptor potential cation channel	Rattus norvegicus	280-284
18306096-5	2008	The AVP-receptor antagonists, including conivaptan, tolvaptan, lixivaptan, and satavaptan, represent a therapeutic advance in the treatment of dilutional hyponatremia.	Tolvaptan	52-61	arginine vasopressin	Homo sapiens	4-7
18037090-0	2007	Tolvaptan, an oral vasopressin V2 receptor antagonist for heart failure?	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	19-42
17703139-0	2007	Pharmacokinetic and pharmacodynamic interaction between tolvaptan, a non-peptide AVP antagonist, and furosemide or hydrochlorothiazide.	Tolvaptan	56-65	arginine vasopressin	Homo sapiens	81-84
17660019-0	2007	Effects of tolvaptan, an oral vasopressin V2 receptor antagonist, in hyponatremia.	Tolvaptan	11-20	arginine vasopressin receptor 2	Homo sapiens	30-53
17703139-9	2007	At 24 hours postdose, plasma renin activity was increased after furosemide or HCTZ administered alone or with tolvaptan, but it was unchanged after tolvaptan alone.	Tolvaptan	110-119	renin	Homo sapiens	29-34
17384437-2	2007	Tolvaptan, a vasopressin V2 receptor blocker, shows promise for management of heart failure.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	13-36
17543634-3	2007	METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the effect of long-term administration of the vasopressin V2-receptor antagonist tolvaptan (30 mg/day) on reducing left ventricular end-diastolic volume (LVEDV) compared with placebo in patients with HF and reduced systolic function, using quantitative radionuclide ventriculography at baseline, repeated after 1 year of therapy, and repeated again approximately 1 week after withdrawal of study drug.	Tolvaptan	187-196	arginine vasopressin receptor 2	Homo sapiens	152-175
17445084-0	2007	Tolvaptan, an orally active vasopressin V(2)-receptor antagonist - pharmacology and clinical trials.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	28-53
17445935-3	2007	We investigated whether tolvaptan, an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis--excretion of electrolyte-free water--might be of benefit in hyponatremia.	Tolvaptan	24-33	arginine vasopressin receptor 2	Homo sapiens	52-77
17445935-13	2007	CONCLUSIONS: In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations at day 4 and day 30.	Tolvaptan	70-79	arginine vasopressin receptor 2	Homo sapiens	89-112
17657988-3	2007	Several AVP receptor antagonists, including tolvaptan and conivaptan, have shown promise in human trials for the treatment of heart failure.	Tolvaptan	44-53	arginine vasopressin	Homo sapiens	8-11
17384438-0	2007	Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.	Tolvaptan	31-40	arginine vasopressin	Homo sapiens	50-61
17384438-2	2007	Tolvaptan, an oral, nonpeptide, selective vasopressin V2-receptor antagonist, shows promise in this condition.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	42-65
17105757-0	2006	Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	28-51
17082233-9	2007	This action of vasopressin was prevented by tolvaptan, a specific V2 receptor antagonist (P < 0.05).	Tolvaptan	44-53	arginine vasopressin	Rattus norvegicus	15-26
16926443-3	2007	We found that the four nonpeptide antagonists SR49059, OPC31260, OPC41061, and SR121463B induced maturation and rescued the BM expression of eight of nine different V2R mutants, stably expressed in physiologically relevant polarized cells.	Tolvaptan	65-73	arginine vasopressin receptor 2	Canis lupus familiaris	165-168
17105757-3	2006	We investigated whether tolvaptan, an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis--excretion of electrolyte-free water--might be of benefit in hyponatremia.	Tolvaptan	24-33	arginine vasopressin receptor 2	Homo sapiens	52-77
17105757-13	2006	CONCLUSIONS: In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations at day 4 and day 30.	Tolvaptan	70-79	arginine vasopressin receptor 2	Homo sapiens	89-112
19804253-1	2006	Tolvaptan is an oral, once-daily nonpeptide arginine vasopressin V(2)-receptor antagonist under development for the treatment of hyponatremia and congestive heart failure.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	53-78
19804253-5	2006	An international Phase III outcome study; Efficacy of Vasopressin antagonism in hEaRt failurE outcome Study with Tolvaptan (EVEREST), evaluating the long-term efficacy and safety of tolvaptan in patients hospitalized with worsening heart failure, is currently ongoing.	Tolvaptan	113-122	arginine vasopressin	Homo sapiens	54-65
16634691-0	2006	Tolvaptan: a selective vasopressin type 2 receptor antagonist in congestive heart failure.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	23-34
16782344-2	2006	This approach was applied to the synthesis of tolvaptan, a very promising vasopressin V2 receptor antagonist currently in clinical trials.	Tolvaptan	46-55	arginine vasopressin receptor 2	Homo sapiens	74-97
16794787-4	2006	The vaptans are vasopressin receptor antagonists with V1a (relcovaptan) or V2 (tolvaptan, lixivaptan) selectivity or non-selective activity (conivaptan) which may be advantageous in some disorders.	Tolvaptan	79-88	arginine vasopressin	Homo sapiens	16-27
16220067-2	2005	Tolvaptan (Otsuka) is an orally administered nonpeptide vasopressin (VP) V2 receptor antagonist that inhibits water reabsorption in the kidney by competitively blocking VP binding, resulting in water diuresis without significantly changing total electrolyte excretion.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	56-84
16563917-0	2006	Vasopressin v(2) receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia.	Tolvaptan	40-49	arginine vasopressin receptor 2	Homo sapiens	0-25
16211205-1	2005	BACKGROUND: Tolvaptan, a nonpeptide selective vasopressin receptor (V2) antagonist, is in development for the treatment of congestive heart failure and hyponatremia.	Tolvaptan	12-21	T cell receptor gamma variable 9	Homo sapiens	46-70
16211205-2	2005	Tolvaptan is primarily metabolized via CYP3A4.	Tolvaptan	0-9	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	39-45
16211205-3	2005	This study was conducted to determine the extent of the pharmacokinetic interaction between tolvaptan and steady state amiodarone, an antiarrhythmic drug commonly prescribed for patients with congestive heart failure and a known inhibitor of other drugs metabolized by CYP3A4.	Tolvaptan	92-101	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	269-275
15926866-3	2005	Results of early trials with tolvaptan (selective vasopressin subtype 2 receptor antagonist) and conivaptan (dual vasopressin subtypes 1a and 2 receptor antagonist) have demonstrated improvement in the fluid status, osmotic balance and haemodynamic profile in patients with heart failure presenting with signs and symptoms of decompensation.	Tolvaptan	29-38	arginine vasopressin	Homo sapiens	50-61
16181825-11	2005	Tolvaptan is a vasopressin V2-receptor antagonist that functions as an aquaretic (ie, it increases urine volume and serum sodium with little or no sodium loss).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	15-38
15831573-0	2005	Therapeutic effects of tolvaptan, a potent, selective nonpeptide vasopressin V2 receptor antagonist, in rats with acute and chronic severe hyponatremia.	Tolvaptan	23-32	arginine vasopressin receptor 2	Rattus norvegicus	65-88
15926874-3	2005	In a recent randomised study, tolvaptan, a novel vasopressin antagonist, in addition to standard therapy including diuretics, increased net fluid loss resulting in decreased body weight more effectively than standard therapy alone in patients hospitalised for heart failure.	Tolvaptan	30-39	arginine vasopressin	Homo sapiens	49-60
15461553-4	2004	In the Acute and Chronic Therapeutic Impact of a Vasopressin antagonist in Congestive Heart Failure trial of patients hospitalised with HF, tolvaptan 30 mg/day increased urine volume and induced a weight loss of 3.3 kg at discharge (placebo; 1.9 kg).	Tolvaptan	140-149	arginine vasopressin	Homo sapiens	49-60
15880334-0	2005	Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST).	Tolvaptan	180-189	arginine vasopressin	Homo sapiens	120-131
15880334-3	2005	Tolvaptan is an oral vasopressin (V 2 ) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	21-32
15880334-4	2005	The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care.	Tolvaptan	75-84	arginine vasopressin	Homo sapiens	16-27
15880334-4	2005	The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care.	Tolvaptan	206-215	arginine vasopressin	Homo sapiens	16-27
15695526-4	2005	Two vasopressin antagonists, in particular, tolvaptan and conivaptan, have shown promise in animal studies and small-scale human trials.	Tolvaptan	44-53	arginine vasopressin	Homo sapiens	4-15
12742979-0	2003	Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial.	Tolvaptan	38-47	arginine vasopressin receptor 2	Homo sapiens	0-23
15113814-0	2004	Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial.	Tolvaptan	11-20	arginine vasopressin	Homo sapiens	24-35
15113814-3	2004	In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function.	Tolvaptan	53-62	arginine vasopressin	Homo sapiens	30-41
35227907-0	2022	Tolvaptan reduces angiotensin II-induced experimental abdominal aortic aneurysm and dissection.	Tolvaptan	0-9	angiotensinogen	Homo sapiens	18-32
33033683-2	2020	A vasopressin V2-receptor antagonist (tolvaptan) was recently approved for the treatment of ADPKD.	Tolvaptan	38-47	arginine vasopressin receptor 2	Homo sapiens	2-25
29453607-0	2018	Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment.	Tolvaptan	128-137	semaphorin 7A (John Milton Hagen blood group)	Homo sapiens	0-13
29453607-10	2018	Compared to tolvaptan-naive ADPKD patients, those treated with tolvaptan showed reduced SEMA7A expression on monocytes, T lymphocytes, and Tregs, although the number of PBMCs was unchanged.	Tolvaptan	63-72	semaphorin 7A (John Milton Hagen blood group)	Homo sapiens	88-94
29453607-11	2018	After 1 month of tolvaptan treatment, SEMA7A expression on Tregs decreased.	Tolvaptan	17-26	semaphorin 7A (John Milton Hagen blood group)	Homo sapiens	38-44
29453607-13	2018	SEMA7A expression was lower after tolvaptan treatment, which may reflect drug efficacy.	Tolvaptan	34-43	semaphorin 7A (John Milton Hagen blood group)	Homo sapiens	0-6
29297709-1	2018	OBJECTIVE: Assess characteristics of patients with heart failure (HF) and hyponatremia (HN) using tolvaptan, a selective vasopressin V2-receptor antagonist, for sodium correction, and estimate the budget impact of tolvaptan use in a hospital.	Tolvaptan	98-107	arginine vasopressin receptor 2	Homo sapiens	121-144
26507107-1	2016	Tolvaptan is a vasopressin V(2)-receptor antagonist that has shown promise in treating Autosomal Dominant Polycystic Kidney Disease (ADPKD).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	15-40
26507107-4	2016	In this study, the ability of tolvaptan and two metabolites, DM-4103 and DM-4107, to inhibit human hepatic transporters (NTCP, BSEP, MRP2, MRP3, and MRP4) and bile acid transport in sandwich-cultured human hepatocytes (SCHH) was explored.	Tolvaptan	30-39	solute carrier family 10 member 1	Homo sapiens	121-125
26507107-4	2016	In this study, the ability of tolvaptan and two metabolites, DM-4103 and DM-4107, to inhibit human hepatic transporters (NTCP, BSEP, MRP2, MRP3, and MRP4) and bile acid transport in sandwich-cultured human hepatocytes (SCHH) was explored.	Tolvaptan	30-39	ATP binding cassette subfamily B member 11	Homo sapiens	127-131
26507107-4	2016	In this study, the ability of tolvaptan and two metabolites, DM-4103 and DM-4107, to inhibit human hepatic transporters (NTCP, BSEP, MRP2, MRP3, and MRP4) and bile acid transport in sandwich-cultured human hepatocytes (SCHH) was explored.	Tolvaptan	30-39	ATP binding cassette subfamily C member 2	Homo sapiens	133-137
26507107-4	2016	In this study, the ability of tolvaptan and two metabolites, DM-4103 and DM-4107, to inhibit human hepatic transporters (NTCP, BSEP, MRP2, MRP3, and MRP4) and bile acid transport in sandwich-cultured human hepatocytes (SCHH) was explored.	Tolvaptan	30-39	ATP binding cassette subfamily C member 3	Homo sapiens	139-143
26507107-4	2016	In this study, the ability of tolvaptan and two metabolites, DM-4103 and DM-4107, to inhibit human hepatic transporters (NTCP, BSEP, MRP2, MRP3, and MRP4) and bile acid transport in sandwich-cultured human hepatocytes (SCHH) was explored.	Tolvaptan	30-39	ATP binding cassette subfamily C member 4	Homo sapiens	149-153
26507107-7	2016	Tolvaptan accumulation in SCHH was extensive and not sodium-dependent; intracellular concentrations were ~500 muM after a 10-min incubation duration with tolvaptan (15 muM).	Tolvaptan	0-9	latexin	Homo sapiens	168-171
26507107-8	2016	The biliary clearance of taurocholic acid (TCA) decreased by 43% when SCHH were co-incubated with tolvaptan (15 muM) and TCA (2.5 muM).	Tolvaptan	98-107	latexin	Homo sapiens	112-115
26507107-8	2016	The biliary clearance of taurocholic acid (TCA) decreased by 43% when SCHH were co-incubated with tolvaptan (15 muM) and TCA (2.5 muM).	Tolvaptan	98-107	latexin	Homo sapiens	130-133
26507107-9	2016	When tolvaptan (15 muM) was co-incubated with 2.5 muM of chenodeoxycholic acid, taurochenodeoxycholic acid, or glycochenodeoxycholic acid in separate studies, the cellular accumulation of these bile acids increased by 1.30-, 1.68-, and 2.16-fold, respectively.	Tolvaptan	5-14	latexin	Homo sapiens	19-22
26507107-9	2016	When tolvaptan (15 muM) was co-incubated with 2.5 muM of chenodeoxycholic acid, taurochenodeoxycholic acid, or glycochenodeoxycholic acid in separate studies, the cellular accumulation of these bile acids increased by 1.30-, 1.68-, and 2.16-fold, respectively.	Tolvaptan	5-14	latexin	Homo sapiens	50-53
34309184-0	2021	A Genome-Wide Association Study Identifying SVEP1 Variant as a Predictor of Response to Tolvaptan for Cirrhotic Ascites.	Tolvaptan	88-97	sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1	Homo sapiens	44-49
34309184-1	2021	BACKGROUND AND AIMS: Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan.	Tolvaptan	21-30	arginine vasopressin receptor 2	Homo sapiens	32-55
34309184-10	2021	CONCLUSION: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response.	Tolvaptan	71-80	sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1	Homo sapiens	12-17
34486176-4	2021	Lixivaptan is expected to have a safer liver profile compared to tolvaptan, the only drug approved to delay PKD progression, based on computational model results and initial clinical evidence.	Tolvaptan	65-74	protein kinase D1	Homo sapiens	108-111
34094612-4	2021	The infant was successfully treated with tolvaptan, a competitive inhibitor of the vasopressin V2 receptor.	Tolvaptan	41-50	arginine vasopressin receptor 2	Homo sapiens	83-106
34955900-6	2021	The upregulation of AQP2 was blocked by the V2R antagonist tolvaptan or protein kinase A (PKA) inhibitors.	Tolvaptan	59-68	aquaporin 2	Homo sapiens	20-24
34955900-6	2021	The upregulation of AQP2 was blocked by the V2R antagonist tolvaptan or protein kinase A (PKA) inhibitors.	Tolvaptan	59-68	arginine vasopressin receptor 2	Homo sapiens	44-47
34884753-8	2021	Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	13-36
34511889-8	2021	During treatment with tolvaptan, the eGFR decreased from 78.8 +- 15.9 mL/min/1.73 m2 to 48.3 +- 19.4 mL/min/1.73 m2 (P < 0.0001).	Tolvaptan	22-31	epidermal growth factor receptor	Homo sapiens	37-41
34480075-1	2021	The vasopressin V2 receptor antagonist tolvaptan delays the progression of autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	4-27
34540466-8	2021	The use of therapeutic agents such as sodium-glucose co-transporter 2 inhibitors and tolvaptan (a vasopressin V2 receptor antagonist), and cardiac resynchronization therapy has also been shown to have potential benefits in managing the disease.	Tolvaptan	85-94	arginine vasopressin receptor 2	Homo sapiens	98-121
34514204-0	2021	Urinary Aquaporin 2 as a Potential Indicator Predicting Tolvaptan Response in Patients With ADPKD.	Tolvaptan	56-65	aquaporin 2	Homo sapiens	8-19
34514204-1	2021	Introduction: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells.	Tolvaptan	14-23	arginine vasopressin	Homo sapiens	150-161
34514204-1	2021	Introduction: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells.	Tolvaptan	14-23	arginine vasopressin receptor 2	Homo sapiens	169-192
34514204-1	2021	Introduction: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells.	Tolvaptan	14-23	arginine vasopressin receptor 2	Homo sapiens	194-197
34514204-1	2021	Introduction: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells.	Tolvaptan	14-23	aquaporin 2	Homo sapiens	244-269
34514204-1	2021	Introduction: Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) because it inhibits binding of the antidiuretic hormone vasopressin to the vasopressin V2 receptor (V2R), which suppresses the insertion of preformed water channel aquaporin 2 (AQP2) molecules in the luminal membrane of the collecting duct cells.	Tolvaptan	14-23	aquaporin 2	Homo sapiens	271-275
34514204-2	2021	Methods: This single-center, prospective observational cohort study investigated whether decreased AQP2 elimination in urine affects the renal prognosis of patients who received tolvaptan.	Tolvaptan	178-187	aquaporin 2	Homo sapiens	99-103
34514204-6	2021	U-AQP2 per milligram of urinary creatinine (U-AQP2/Cr) decreased from 67.8 +- 50.6 to 20.7 +- 15.1 fmol/mg urinary creatinine after 1 month of tolvaptan treatment.	Tolvaptan	143-152	aquaporin 2	Homo sapiens	2-6
34514204-6	2021	U-AQP2 per milligram of urinary creatinine (U-AQP2/Cr) decreased from 67.8 +- 50.6 to 20.7 +- 15.1 fmol/mg urinary creatinine after 1 month of tolvaptan treatment.	Tolvaptan	143-152	aquaporin 2	Homo sapiens	46-50
34514204-9	2021	Conclusion: Initial decrease in U-AQP2/Cr in the first month of treatment reflects the pharmacologic effect of tolvaptan and could be an indicator of renal prognosis during tolvaptan treatment.	Tolvaptan	111-120	aquaporin 2	Homo sapiens	34-38
34234441-2	2021	Tolvaptan is a selective vasopressin antagonist and has emerged as a promising therapeutic option for patients with autosomal dominant polycystic kidney disease.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	25-36
34070416-1	2021	Tolvaptan is a recently available diuretic that blocks arginine vasopressin receptor 2 in the renal collecting duct.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	55-86
34719623-0	2021	Serum Copeptin and Zinc-alpha2-glycoprotein Levels Are Novel Biomarkers of Tolvaptan Treatment in Decompensated Cirrhotic Patients with Ascites.	Tolvaptan	75-84	arginine vasopressin	Homo sapiens	6-14
34719623-0	2021	Serum Copeptin and Zinc-alpha2-glycoprotein Levels Are Novel Biomarkers of Tolvaptan Treatment in Decompensated Cirrhotic Patients with Ascites.	Tolvaptan	75-84	alpha-2-glycoprotein 1, zinc-binding	Homo sapiens	19-43
34719623-1	2021	Objective The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with massive ascites unresponsive to conventional diuretics.	Tolvaptan	26-35	arginine vasopressin receptor 2	Homo sapiens	54-77
34719623-11	2021	Conclusion Serum BUN, copeptin and ZAG levels predict the patient response to tolvaptan, even when measured prior to treatment.	Tolvaptan	78-87	arginine vasopressin	Homo sapiens	22-30
34719623-11	2021	Conclusion Serum BUN, copeptin and ZAG levels predict the patient response to tolvaptan, even when measured prior to treatment.	Tolvaptan	78-87	alpha-2-glycoprotein 1, zinc-binding	Homo sapiens	35-38
35050407-2	2022	Tolvaptan (TLV), a vasopressin V2 receptor inhibitor, is effective in controlling decompensated HF.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	19-42
35050407-2	2022	Tolvaptan (TLV), a vasopressin V2 receptor inhibitor, is effective in controlling decompensated HF.	Tolvaptan	11-14	arginine vasopressin receptor 2	Homo sapiens	19-42
35050407-11	2022	During the follow-up, the severity of TR improved in the TLV group (trivial-mild: 52.6%; moderate: 36.8%; severe: 10.5%) (p < 0.01).	Tolvaptan	57-60	coagulation factor II thrombin receptor	Homo sapiens	38-40
35165806-1	2022	BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD).	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	25-48
35227907-5	2022	In vitro study showed that tolvaptan suppressed matrix metalloproteinase (MMP) expressions (MMP-2 and MMP-9) and apoptosis in Ang II-stimulated HASMCs.	Tolvaptan	27-36	matrix metallopeptidase 2	Homo sapiens	92-97
35227907-5	2022	In vitro study showed that tolvaptan suppressed matrix metalloproteinase (MMP) expressions (MMP-2 and MMP-9) and apoptosis in Ang II-stimulated HASMCs.	Tolvaptan	27-36	matrix metallopeptidase 9	Homo sapiens	102-107
35227907-8	2022	Specifically, tolvaptan reduced the expression of receptor-interacting protein kinase 3 (RIP3) and decreased apoptosis of SMCs.	Tolvaptan	14-23	receptor interacting serine/threonine kinase 3	Homo sapiens	50-87
35227907-8	2022	Specifically, tolvaptan reduced the expression of receptor-interacting protein kinase 3 (RIP3) and decreased apoptosis of SMCs.	Tolvaptan	14-23	receptor interacting serine/threonine kinase 3	Homo sapiens	89-93
35227907-9	2022	Our data demonstrated that tolvaptan reduces experimental AAA formation and dissection by inhibiting destruction of the aortic structure integrity and reducing inflammatory macrophage infiltration, MMP-2 and MMP-9 expressions, and apoptosis of vascular SMCs, indicating tolvaptan may have therapeutic potential for AAA and dissection.	Tolvaptan	27-36	matrix metallopeptidase 2	Homo sapiens	198-203
35604424-0	2022	Stereoselective interaction of tolvaptan with amiodarone under racemic metabolic impact by CYP3A5 genotypes in heart failure patients.	Tolvaptan	31-40	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	91-97
35227907-9	2022	Our data demonstrated that tolvaptan reduces experimental AAA formation and dissection by inhibiting destruction of the aortic structure integrity and reducing inflammatory macrophage infiltration, MMP-2 and MMP-9 expressions, and apoptosis of vascular SMCs, indicating tolvaptan may have therapeutic potential for AAA and dissection.	Tolvaptan	27-36	matrix metallopeptidase 9	Homo sapiens	208-213
35604424-1	2022	PURPOSE: The diuretic effect of tolvaptan is largely blood level-dependent although it does exhibit interindividual differences according to cytochrome P450 (CYP) 3A5 genotype.	Tolvaptan	32-41	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	141-166
35585803-3	2022	CASE PRESENTATION: This report describes the case of an asymptomatic patient with TSC2/PKD1 contiguous gene syndrome that fulfills the imaging criteria for initiating the treatment with tolvaptan.	Tolvaptan	186-195	TSC complex subunit 2	Homo sapiens	82-86
35604424-8	2022	CYP3A5 genotypes significantly affected the concentration ratio of all enantiomeric metabolites to tolvaptan, while the other metabolic-related gene polymorphisms had no influence.	Tolvaptan	99-108	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	0-6
35604424-9	2022	A negative correlation was found between serum albumin and the enantiomeric ratio of tolvaptan and monohydroxylate DM-4111.	Tolvaptan	85-94	albumin	Homo sapiens	41-54
35604424-11	2022	5S-tolvaptan was selectively synthesized from ketone MOP-21826 by CBR1 with a substantially smaller reaction velocity compared to tolvaptan monohydroxylation by CYP3A4/5.	Tolvaptan	130-139	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	161-169
35604424-12	2022	CONCLUSION: This study clarified the racemic impact of CYP3A5 genotypes on tolvaptan metabolism.	Tolvaptan	75-84	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	55-61
35604542-4	2022	Tolvaptan, a selective vasopressin receptor type 2 (V2) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis.	Tolvaptan	0-9	T cell receptor gamma variable 9	Homo sapiens	23-54
35604542-13	2022	Accordingly, tolvaptan counteracted the RhoA/ROCK1-2 pathway, which has a pivotal role in regulating cell movement.	Tolvaptan	13-22	ras homolog family member A	Homo sapiens	40-44
35604542-13	2022	Accordingly, tolvaptan counteracted the RhoA/ROCK1-2 pathway, which has a pivotal role in regulating cell movement.	Tolvaptan	13-22	Rho associated coiled-coil containing protein kinase 1	Homo sapiens	45-52
35585803-5	2022	CONCLUSION: In this TSC2/PKD1 contiguous gene syndrome single case report, tolvaptan was safe and well-tolerated.	Tolvaptan	75-84	TSC complex subunit 2	Homo sapiens	20-24
35503085-6	2022	By contrast, blocking AVPR2 with a selective FDA-approved antagonist, Tolvaptan, reduced cell growth.	Tolvaptan	70-79	arginine vasopressin receptor 2	Homo sapiens	22-27
35110480-1	2022	Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid.	Tolvaptan	10-19	arginine vasopressin receptor 2	Homo sapiens	23-46
35472391-3	2022	METHODS: Using data from 4,133 patients from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial, we used multivariable Cox regression models to evaluate the association between rates of in-hospital change in assessments of volume overload, including b-type natriuretic peptide (BNP), N-terminal pro b-type natriuretic peptide (NT-proBNP), as well as change in hemoconcentration, with risk of all-cause mortality and a composite outcome of cardiovascular mortality or heart failure hospitalization.	Tolvaptan	120-129	arginine vasopressin	Homo sapiens	61-72
35470999-6	2022	p22 phox protein expression was lower in tolvaptan treated ADPKD and controls compared to untreated patients: 0.86 +-0.15 d.u.	Tolvaptan	41-50	cytochrome b-245 alpha chain	Homo sapiens	0-8
35314480-1	2022	BACKGROUND AND OBJECTIVES: The vasopressin V2 receptor antagonist tolvaptan is the only drug that has been proven to be nephroprotective in autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	66-75	arginine vasopressin receptor 2	Homo sapiens	31-54
35134221-1	2022	The approval of the vasopressin V2-receptor antagonist tolvaptan - based on the landmark TEMPO 3:4 trial - has marked a transformation in the management of autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	55-64	arginine vasopressin receptor 2	Homo sapiens	20-43
35428556-3	2022	Major points of the CP were as follows: using tolvaptan as a standard therapy, completing the acute therapies within three days, and starting cardiac rehabilitation from the second day after admission.	Tolvaptan	46-55	ceruloplasmin	Homo sapiens	20-22
35428556-9	2022	Use of the CP was an independent negative factor contributing to LOHS for patients with ADHF, even after adjustment of other factors including the use of tolvaptan (p < 0.001).	Tolvaptan	154-163	ceruloplasmin	Homo sapiens	11-13
34039465-3	2021	Tolvaptan (TVP), a vasopressin V2 receptor antagonist, has a favorable profile in terms of rapid fluid removal and less aggravation of renal function.	Tolvaptan	11-14	arginine vasopressin receptor 2	Homo sapiens	19-42
32901255-2	2021	This randomized, double-blind, placebo-controlled, Phase 2 trial evaluated the efficacy and safety of tolvaptan, a vasopressin V2 receptor antagonist, in Japanese HD patients.	Tolvaptan	102-111	arginine vasopressin receptor 2	Homo sapiens	115-138
34039465-3	2021	Tolvaptan (TVP), a vasopressin V2 receptor antagonist, has a favorable profile in terms of rapid fluid removal and less aggravation of renal function.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	19-42
35371438-0	2022	Raynaud"s phenomenon triggered by the vasopressin V2 receptor antagonist tolvaptan in a patient with autosomal dominant polycystic kidney disease and Sjogren"s syndrome.	Tolvaptan	73-82	arginine vasopressin receptor 2	Homo sapiens	38-61
33843270-9	2021	AQP2 membrane trafficking was induced by haloperidol, sertraline, or carbamazepine and was also blocked by cotreatment with tolvaptan or a PKA inhibitor.	Tolvaptan	124-133	aquaporin 2	Rattus norvegicus	0-4
33639694-0	2021	Tolvaptan reduces the required amount of albumin infusion in patients with decompensated cirrhosis with uncontrolled ascites : a multicenter retrospective propensity score-matched cohort study.	Tolvaptan	0-9	albumin	Homo sapiens	41-48
33904139-1	2021	Tolvaptan (TLV) is a vasopressin V2 receptor antagonist that increases free water excretion.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	21-44
33904139-1	2021	Tolvaptan (TLV) is a vasopressin V2 receptor antagonist that increases free water excretion.	Tolvaptan	11-14	arginine vasopressin receptor 2	Homo sapiens	21-44
33920088-0	2021	Regulation of Serum Sodium Levels during Chemotherapy Using Selective Arginine Vasopressin V2-Receptor Antagonist Tolvaptan in a Four-Year-Old Girl with a Suprasellar Germ Cell Tumor.	Tolvaptan	114-123	arginine vasopressin receptor 2	Homo sapiens	79-102
32779125-0	2021	Expression of aquaporin-2 in the collecting duct and responses to tolvaptan.	Tolvaptan	66-75	aquaporin 2	Homo sapiens	14-25
32779125-3	2021	While the expression of aquaporin-2 might be a key to response to tolvaptan, detailed mechanism of refractoriness to tolvaptan remains unknown.	Tolvaptan	66-75	aquaporin 2	Homo sapiens	24-35
32779125-7	2021	Inactivated aquaporin-2 expression in the collecting duct, which was for example caused by pre-clinical urinary infection as our latter case, might have an association with refractoriness to tolvaptan.	Tolvaptan	191-200	aquaporin 2	Homo sapiens	12-23
32748396-5	2021	In vitro experiments (C-DILI ) with sandwich-cultured human hepatocytes and HepaRG  cells were performed to assess tolvaptan-associated hepatotoxic effects when MRP2 was impaired by chemical inhibition (MK571, 50microM) or genetic knockout, respectively.	Tolvaptan	115-124	ATP binding cassette subfamily C member 2	Homo sapiens	161-165
32748396-6	2021	Tolvaptan (64microM, 24hr) treatment of these cells increased cytotoxicity markers up to 27.9-fold and 1.6-fold, respectively, when MRP2 was impaired, indicating that MRP2 dysfunction may be involved in tolvaptan-associated cytotoxicity.	Tolvaptan	0-9	ATP binding cassette subfamily C member 2	Homo sapiens	132-136
33022361-8	2021	Time- and concentration-dependent decreases in ATP and albumin were observed in response to the DILI-causing drugs acetaminophen, fialuridine, AMG-009, and tolvaptan.	Tolvaptan	156-165	albumin	Mus musculus	55-62
33843270-10	2021	Furthermore, upregulation of V2R and AQP2 mRNA and phosphorylated CREB was induced by haloperidol, sertraline, or carbamazepine and was blocked by tolvaptan cotreatment.	Tolvaptan	147-156	aquaporin 2	Rattus norvegicus	37-41
33843270-10	2021	Furthermore, upregulation of V2R and AQP2 mRNA and phosphorylated CREB was induced by haloperidol, sertraline, or carbamazepine and was blocked by tolvaptan cotreatment.	Tolvaptan	147-156	cAMP responsive element binding protein 1	Rattus norvegicus	66-70
33742787-2	2021	In vitro, tolvaptan was a breast cancer resistance protein (BCRP) inhibitor while the oxobutyric acid metabolite of tolvaptan (DM-4013) was an inhibitor of organic anion transport polypeptide (OATP) 1B1 and organic anion transporter (OAT) 3.	Tolvaptan	10-19	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	26-58
33742787-2	2021	In vitro, tolvaptan was a breast cancer resistance protein (BCRP) inhibitor while the oxobutyric acid metabolite of tolvaptan (DM-4013) was an inhibitor of organic anion transport polypeptide (OATP) 1B1 and organic anion transporter (OAT) 3.	Tolvaptan	10-19	ATP binding cassette subfamily G member 2 (Junior blood group)	Homo sapiens	60-64
33742787-2	2021	In vitro, tolvaptan was a breast cancer resistance protein (BCRP) inhibitor while the oxobutyric acid metabolite of tolvaptan (DM-4013) was an inhibitor of organic anion transport polypeptide (OATP) 1B1 and organic anion transporter (OAT) 3.	Tolvaptan	116-125	solute carrier organic anion transporter family member 1B1	Homo sapiens	156-202
33742787-2	2021	In vitro, tolvaptan was a breast cancer resistance protein (BCRP) inhibitor while the oxobutyric acid metabolite of tolvaptan (DM-4013) was an inhibitor of organic anion transport polypeptide (OATP) 1B1 and organic anion transporter (OAT) 3.	Tolvaptan	116-125	solute carrier family 22 member 8	Homo sapiens	207-240
33693944-6	2021	Following an initial dose of tolvaptan 7.5 mg, median (range) increase in sNa observed at 24 hours was 9(1-19) mmol/L.	Tolvaptan	29-38	snail family transcriptional repressor 1	Homo sapiens	74-77
33693944-10	2021	The rate of sNa correction in the first 24 hours was significantly higher among participants that continued fluid restriction after tolvaptan administration (median[quantiles]: 14[9-16] versus 8[5-11] mmol/L, p=0.036).	Tolvaptan	132-141	snail family transcriptional repressor 1	Homo sapiens	12-15
33555573-14	2022	Remission of palmar hyperhidrosis is probably mediated by tolvaptan acting on central ACTH secretion.	Tolvaptan	58-67	proopiomelanocortin	Homo sapiens	86-90
32748396-6	2021	Tolvaptan (64microM, 24hr) treatment of these cells increased cytotoxicity markers up to 27.9-fold and 1.6-fold, respectively, when MRP2 was impaired, indicating that MRP2 dysfunction may be involved in tolvaptan-associated cytotoxicity.	Tolvaptan	0-9	ATP binding cassette subfamily C member 2	Homo sapiens	167-171
32748396-6	2021	Tolvaptan (64microM, 24hr) treatment of these cells increased cytotoxicity markers up to 27.9-fold and 1.6-fold, respectively, when MRP2 was impaired, indicating that MRP2 dysfunction may be involved in tolvaptan-associated cytotoxicity.	Tolvaptan	203-212	ATP binding cassette subfamily C member 2	Homo sapiens	167-171
32748396-7	2021	In conclusion, QST modeling supported the hypothesis that reduced biliary efflux of tolvaptan and/or DM-4103 could account for increased susceptibility to tolvaptan-associated hepatotoxicity; in vitro experiments implicated MRP2 dysfunction as a key factor in susceptibility.	Tolvaptan	84-93	ATP binding cassette subfamily C member 2	Homo sapiens	224-228
32748396-9	2021	ADPKD progression and gradual reduction in MRP2 activity may explain why acute liver events can occur well after one year of tolvaptan treatment.	Tolvaptan	125-134	ATP binding cassette subfamily C member 2	Homo sapiens	43-47
33639694-1	2021	Background: The aim of this retrospective study was to determine whether tolvaptan treatment reduces the amount of albumin administered, volume of ascites removed, and frequency of paracentesis procedures in patients with decompensated cirrhosis with uncontrolled ascites with conventional diuretics.	Tolvaptan	73-82	albumin	Homo sapiens	115-122
33639694-9	2021	Conclusions: Tolvaptan reduced the use of albumin infusion in patients with decompensated cirrhosis and was effective and acceptable for uncontrolled ascites.	Tolvaptan	13-22	albumin	Homo sapiens	42-49
33208569-0	2020	Daily Monitoring of Serum Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein Is Useful for Predicting Therapeutic Effect of Tolvaptan in Cirrhotic Ascites.	Tolvaptan	135-144	galectin 3 binding protein	Homo sapiens	66-87
33518649-0	2021	[Retrospective Observational Study on Predictors of Body Weight and BNP Teduction in Cases of Tolvaptan Induction for Heart Failure].	Tolvaptan	94-103	natriuretic peptide B	Homo sapiens	68-71
33518649-11	2021	Therefore, it was suggested that urine sodium concentration may be useful as a predictor of body weight and BNP decrease after TLV induction.	Tolvaptan	127-130	natriuretic peptide B	Homo sapiens	108-111
33308138-4	2020	Several clinical trials with a variety of drugs have failed, and the only Food and Drugs Administration (FDA) approved drug to treat ADPKD to date is tolvaptan that works by antagonizing the vasopressin-2 receptor (V2R).	Tolvaptan	150-159	arginine vasopressin receptor 2	Homo sapiens	191-218
33208569-2	2020	Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	29-52
33208569-2	2020	Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established.	Tolvaptan	11-14	arginine vasopressin receptor 2	Homo sapiens	29-52
33208569-11	2020	The ratio of WFA+-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05).	Tolvaptan	45-48	galectin 3 binding protein	Homo sapiens	18-22
33208569-13	2020	In conclusion, monitoring serum WFA+-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.	Tolvaptan	84-87	galectin 3 binding protein	Homo sapiens	37-41
32665162-0	2020	Differences in pharmacological property between combined therapy of the vasopressin V2-receptor antagonist tolvaptan plus furosemide and monotherapy of furosemide in patients with hospitalized heart failure.	Tolvaptan	107-116	arginine vasopressin receptor 2	Homo sapiens	72-95
33009446-0	2020	Characterization of five novel vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus reveals a role of tolvaptan for M272R-V2R mutation.	Tolvaptan	120-129	arginine vasopressin receptor 2	Canis lupus familiaris	31-54
33009446-0	2020	Characterization of five novel vasopressin V2 receptor mutants causing nephrogenic diabetes insipidus reveals a role of tolvaptan for M272R-V2R mutation.	Tolvaptan	120-129	arginine vasopressin receptor 2	Canis lupus familiaris	140-143
33009446-7	2020	In order to rescue the function of the mutated V2R, we tested VX-809, sildenafil citrate, ibuprofen and tolvaptan in MDCK cells.	Tolvaptan	104-113	arginine vasopressin receptor 2	Canis lupus familiaris	47-50
33009446-9	2020	These results show an important proof of concept for the use of tolvaptan in patients affected by M272R mutation of V2R causing NDI.	Tolvaptan	64-73	arginine vasopressin receptor 2	Homo sapiens	116-119
32527945-6	2020	Unadjusted and multivariable mixed-effects linear regression models, adjusted for age, sex, body mass index, eGFR, net acid excretion, and height-adjusted total kidney volume, were used to assess the association of Tolvaptan with urinary parameters relevant for kidney stone formation.	Tolvaptan	215-224	epidermal growth factor receptor	Homo sapiens	109-113
32996719-5	2020	Tolvaptan (TOL) is a selective vasopressin V2 receptor antagonist used in the treatment of clinically significant hyponatremia, volume overload in heart failure, and liver cirrhosis with edema.	Tolvaptan	0-9	arginine vasopressin receptor 2	Rattus norvegicus	31-54
32996719-5	2020	Tolvaptan (TOL) is a selective vasopressin V2 receptor antagonist used in the treatment of clinically significant hyponatremia, volume overload in heart failure, and liver cirrhosis with edema.	Tolvaptan	11-14	arginine vasopressin receptor 2	Rattus norvegicus	31-54
32996719-11	2020	Also, co-treatment with TOL significantly decreased the level of markers of apoptosis as caspase-3 and Bax with increased expression of antiapoptotic Bcl-2 in renal tissue as compared to CP-treated group.	Tolvaptan	24-27	caspase 3	Rattus norvegicus	89-98
32996719-11	2020	Also, co-treatment with TOL significantly decreased the level of markers of apoptosis as caspase-3 and Bax with increased expression of antiapoptotic Bcl-2 in renal tissue as compared to CP-treated group.	Tolvaptan	24-27	BCL2 associated X, apoptosis regulator	Rattus norvegicus	103-106
32996719-11	2020	Also, co-treatment with TOL significantly decreased the level of markers of apoptosis as caspase-3 and Bax with increased expression of antiapoptotic Bcl-2 in renal tissue as compared to CP-treated group.	Tolvaptan	24-27	BCL2, apoptosis regulator	Rattus norvegicus	150-155
32683063-0	2020	Pharmacological dilutional therapy using the vasopressin antagonist tolvaptan for young patients with cystinuria: a pilot investigation.	Tolvaptan	68-77	arginine vasopressin	Homo sapiens	45-56
32683063-1	2020	OBJECTIVE: To perform a pilot study of short-term safety, tolerability, and impact on urinary stone risk parameters of the vasopressin V2-receptor antagonist tolvaptan (which increases urinary excretion of free water) among adolescents and young adults with cystinuria.	Tolvaptan	158-167	arginine vasopressin receptor 2	Homo sapiens	123-146
32684555-4	2020	In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times).	Tolvaptan	127-136	albumin	Homo sapiens	9-16
32684555-4	2020	In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times).	Tolvaptan	127-136	albumin	Homo sapiens	174-181
32335259-4	2020	Tolvaptan, a vasopressin V2 receptor antagonist is the first drug approved by regulatory agencies to treat rapidly progressive ADPKD.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	13-36
32957887-2	2021	In 2017, the Italian Medicines Agency authorised tolvaptan, a vasopressin V2 receptor antagonist, for the treatment of ADPKD, based on the Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO 3: 4), TEMPO 4: 4 and Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) studies.	Tolvaptan	49-58	arginine vasopressin receptor 2	Homo sapiens	62-85
32543020-7	2020	Cystatin C improved at 24 h with tolvaptan compared with furosemide (-6.4 +- 11.8 vs. 4.1 +- 17.2% change, P = 0.036), but the effect was transient.	Tolvaptan	33-42	cystatin C	Homo sapiens	0-10
32543020-9	2020	Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide.	Tolvaptan	57-66	arginine vasopressin	Homo sapiens	25-33
32535124-3	2020	METHODS: Using data from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) trial, we used multivariable Cox regression models to evaluate the association between in-hospital changes in estimated glomerular filtration rate (eGFR) with death and a composite outcome of cardiovascular death and hospitalization for heart failure.	Tolvaptan	109-118	arginine vasopressin	Homo sapiens	50-61
32232633-1	2020	BACKGROUND: Tolvaptan is a selective oral vasopressin V2-receptor antagonist.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	42-65
32734960-0	2020	Erratum Regarding "Equivalent Efficacy and Decreased Rate of Overcorrection in Patients With Syndrome of Inappropriate Secretion of Antidiuretic Hormone Given Very Low-Dose Tolvaptan" (Kid Med.	Tolvaptan	173-182	arginine vasopressin	Homo sapiens	132-152
32166738-10	2020	This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.	Tolvaptan	80-89	polycystin 1, transient receptor potential channel interacting	Homo sapiens	41-45
32166738-10	2020	This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.	Tolvaptan	80-89	solute carrier family 2 member 9	Homo sapiens	50-56
32518862-1	2020	Introduction: Tolvaptan, a treatment for autosomal dominant polycystic kidney disease (ADPKD), inhibits vasopressin V2 receptor signaling, which causes aquaretic adverse events (AAEs).	Tolvaptan	14-23	arginine vasopressin receptor 2	Homo sapiens	104-127
31652395-0	2020	Impact of CYP3A5 genotype on tolvaptan pharmacokinetics and their relationships with endogenous markers of CYP3A activity and serum sodium level in heart failure patients.	Tolvaptan	29-38	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	10-16
31652395-2	2020	This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients.	Tolvaptan	76-85	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	46-52
31652395-2	2020	This study aimed to evaluate the influence of CYP3A5 and ABCB1 genotypes on tolvaptan pharmacokinetics and their relationships with plasma markers of CYP3A activity and laboratory test values in heart failure patients.	Tolvaptan	76-85	ATP binding cassette subfamily B member 1	Homo sapiens	57-62
31652395-6	2020	The CYP3A5*3/*3 genotype was associated with a higher plasma concentration of tolvaptan but not with its metabolic ratios.	Tolvaptan	78-87	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	4-10
31652395-9	2020	In a stratified analysis based on CYP3A5 genotype, plasma 4beta-OHC/TC had a negative correlation with plasma tolvaptan concentration in the patients with the CYP3A5*1 allele, while the plasma concentration of 25-OHD did not.	Tolvaptan	110-119	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	159-165
31652395-12	2020	In conclusion, CYP3A5*3 but not ABCB1 genotypes elevated tolvaptan plasma exposure in heart failure patients.	Tolvaptan	57-66	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	15-21
31652395-13	2020	CYP3A5-deficient patients treated with tolvaptan had a higher serum sodium level.	Tolvaptan	39-48	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	0-6
31652395-14	2020	The CYP3A5 genotype altered the relationship between plasma tolvaptan and 4beta-OHC.	Tolvaptan	60-69	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	4-10
30669168-9	2020	The vasopressin receptor 2 antagonist Tolvaptan inhibited desmopressin-induced ACTH secretion in a dose-dependent manner.	Tolvaptan	38-47	pro-opiomelanocortin-alpha	Mus musculus	79-83
31323125-7	2020	CONCLUSIONS: The present findings suggest bodyweight, BUN, C-reactive protein, and hepatitis C as potential predictive factors of tolvaptan short-term response in patients with refractory ascites.	Tolvaptan	130-139	C-reactive protein	Homo sapiens	59-77
32138675-2	2020	Tolvaptan, an orally available, selective vasopressin V2-receptor antagonist approved for hyponatremia in the United States and European Union.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	42-65
32232055-1	2020	Tolvaptan, a vasopressin V<sub>2</sub> receptor antagonist, was initially approved in Japan for treatment of autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	13-24
32995715-1	2020	Background: The Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) score has proven useful for risk prediction in acute decompensated heart failure (ADHF).	Tolvaptan	88-97	arginine vasopressin	Homo sapiens	28-39
31616061-5	2020	In vitro, V2R antagonists OPC31260 and Tolvaptan, or V2R gene silencing reduced wound closure and cell viability of 786-O and Caki-1 human ccRCC cell lines.	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	10-13
31616061-11	2020	These results provide novel evidence for a pathogenic role of V2R signaling in ccRCC, and suggest that inhibitors of the AVP-V2R pathway, including the FDA-approved drug Tolvaptan, could be utilized as novel ccRCC therapeutics.	Tolvaptan	170-179	arginine vasopressin receptor 2	Homo sapiens	62-65
31909447-2	2020	The vasopressin V2 receptor antagonist tolvaptan is approved in multiple countries for the treatment of ADPKD, however its use is associated with clinically significant drug-induced liver injury.	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	4-27
32784291-2	2020	The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature.	Tolvaptan	114-123	polycystin 1, transient receptor potential channel interacting	Homo sapiens	71-75
32784291-2	2020	The influence of mutations in polycystic kidney disease 1 and 2 genes (PKD1 and PKD2) on the treatment effects of tolvaptan is not well documented in the literature.	Tolvaptan	114-123	polycystin 2, transient receptor potential cation channel	Homo sapiens	80-84
32784291-6	2020	Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in DeltaeGFR/y with tolvaptan (0.6 vs. -0.7 mL/min/1.73 m2, respectively; p = 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (-6.7 vs. -1.1%, respectively; p = 0.02).	Tolvaptan	154-163	polycystin 1, transient receptor potential channel interacting	Homo sapiens	45-51
32784291-6	2020	Compared with the group of patients with any PKD1/2 mutation, the group with no PKD1/2 mutation showed significantly less improvement in DeltaeGFR/y with tolvaptan (0.6 vs. -0.7 mL/min/1.73 m2, respectively; p = 0.01) and significantly less improvement in the annual rate of increase in total kidney volume (TKV) with tolvaptan (-6.7 vs. -1.1%, respectively; p = 0.02).	Tolvaptan	154-163	polycystin 1, transient receptor potential channel interacting	Homo sapiens	80-86
32784291-7	2020	CONCLUSION: Patients with ADPKD and no PKD1/2 mutation showed less improvement in DeltaeGFR/y and the annual rate of increase in TKV with tolvaptan.	Tolvaptan	138-147	polycystin 1, transient receptor potential channel interacting	Homo sapiens	39-45
32784291-8	2020	Detecting PKD1/2 mutations may be useful for predicting the effectiveness of tolvaptan.	Tolvaptan	77-86	polycystin 1, transient receptor potential channel interacting	Homo sapiens	10-16
32734225-0	2020	Equivalent Efficacy and Decreased Rate of Overcorrection in Patients With Syndrome of Inappropriate Secretion of Antidiuretic Hormone Given Very Low-Dose Tolvaptan.	Tolvaptan	154-163	arginine vasopressin	Homo sapiens	113-133
31161520-0	2019	Impact of serum albumin levels on the body fluid response to tolvaptan in chronic kidney disease patients.	Tolvaptan	61-70	albumin	Homo sapiens	16-23
31484861-1	2019	Tolvaptan, a vasopressin V2 receptor antagonist, is approved in Japan for the treatment of fluid retention in patients with heart failure (HF), and in the United States for hyponatremia.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	13-36
31161520-1	2019	PURPOSE: Tolvaptan exerts an aquaretic effect by blocking vasopressin V2 receptor.	Tolvaptan	9-18	arginine vasopressin receptor 2	Homo sapiens	58-81
31161520-10	2019	CONCLUSIONS: Serum albumin levels predict the body fluid response to tolvaptan in CKD patients.	Tolvaptan	69-78	albumin	Homo sapiens	19-26
30578654-9	2019	CONCLUSION: Sodium-glucose cotransporter 2 inhibitor DAPA predominantly decreased the ECW with a mild increase in urine volume, but the change in the ECW/total body water was smaller than that in patients treated with FR, and larger than that in patients treated with TLV, suggesting that the effects of SGLT2 inhibitors on fluid distribution may differ from those of conventional diuretics.	Tolvaptan	268-271	solute carrier family 5 member 2	Homo sapiens	12-42
31296836-1	2019	BACKGROUND In the setting of acute decompensated heart failure (ADHF), tolvaptan, a selective V2 receptor antagonist, did not alter plasma renin activity or angiotensin II level, but significantly increased plasma aldosterone by the activation of V1a receptor, suggesting that a high-dose mineralocorticoid receptor antagonist (MRA) combined with a V2 receptor antagonist might be of interest, especially in ADHF patients.	Tolvaptan	71-80	nuclear receptor subfamily 3 group C member 2	Homo sapiens	289-315
31434432-7	2019	The results of immunohistochemistry staining showed that the mean optical density (MOD) of ERK, p-ERK and MMP-9 were significantly increased (all P&lt;0.05), the MOD of Spry1 and PTEN were significantly decreased (both P&lt;0.05), above changes could be significantly reversed by cotreatment with tolvaptan.	Tolvaptan	297-306	Eph receptor B1	Rattus norvegicus	91-94
31434432-11	2019	Conclusions: CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA-21/Spry1/ERK/MMP-9 and miRNA-21/PTEN/PI3K/AKT signaling pathways.	Tolvaptan	101-110	sprouty RTK signaling antagonist 1	Rattus norvegicus	148-153
31434432-11	2019	Conclusions: CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA-21/Spry1/ERK/MMP-9 and miRNA-21/PTEN/PI3K/AKT signaling pathways.	Tolvaptan	101-110	Eph receptor B1	Rattus norvegicus	154-157
31434432-11	2019	Conclusions: CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA-21/Spry1/ERK/MMP-9 and miRNA-21/PTEN/PI3K/AKT signaling pathways.	Tolvaptan	101-110	matrix metallopeptidase 9	Rattus norvegicus	158-163
31434432-11	2019	Conclusions: CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA-21/Spry1/ERK/MMP-9 and miRNA-21/PTEN/PI3K/AKT signaling pathways.	Tolvaptan	101-110	phosphatase and tensin homolog	Rattus norvegicus	177-181
31434432-11	2019	Conclusions: CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA-21/Spry1/ERK/MMP-9 and miRNA-21/PTEN/PI3K/AKT signaling pathways.	Tolvaptan	101-110	AKT serine/threonine kinase 1	Rattus norvegicus	187-190
30703371-6	2019	What"s more, tolvaptan increased the expression of ZO-1 and occludin (p &lt; 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9.	Tolvaptan	13-22	tight junction protein 1	Rattus norvegicus	51-68
30703371-6	2019	What"s more, tolvaptan increased the expression of ZO-1 and occludin (p &lt; 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9.	Tolvaptan	13-22	matrix metallopeptidase 9	Rattus norvegicus	168-173
30703371-6	2019	What"s more, tolvaptan increased the expression of ZO-1 and occludin (p &lt; 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9.	Tolvaptan	155-164	tight junction protein 1	Rattus norvegicus	51-68
30898339-0	2019	Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease.	Tolvaptan	55-64	arginine vasopressin	Homo sapiens	7-15
30898339-1	2019	In the TEMPO 3:4 Trial, treatment with tolvaptan, a vasopressin V2 receptor antagonist, slowed the increase in total kidney volume and decline in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	39-48	arginine vasopressin receptor 2	Homo sapiens	52-75
30898339-6	2019	In tolvaptan-treated subjects, copeptin increased from baseline to week 3 (6.3 pmol/L versus 21.9 pmol/L, respectively).	Tolvaptan	3-12	arginine vasopressin	Homo sapiens	31-39
30898339-7	2019	In tolvaptan-treated subjects with higher baseline copeptin levels, a larger treatment effect was noted with respect to kidney growth rate and eGFR decline.	Tolvaptan	3-12	arginine vasopressin	Homo sapiens	51-59
30898339-8	2019	Tolvaptan-treated subjects with a larger percentage increase in copeptin from baseline to week 3 had a better disease outcome, with less kidney growth and eGFR decline after three years.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	64-72
31239473-0	2019	Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation.	Tolvaptan	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	24-28
31239473-0	2019	Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation.	Tolvaptan	0-9	heme oxygenase 1	Mus musculus	29-33
31239473-0	2019	Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation.	Tolvaptan	0-9	eukaryotic translation initiation factor 2 alpha kinase 3	Mus musculus	62-66
31239473-6	2019	Tolvaptan activated Nrf2 and increased mRNA and protein expression of antioxidant enzyme heme oxygenase-1 (HO-1) in mpkCCD cells and the outer medulla of mouse kidneys.	Tolvaptan	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	20-24
31239473-6	2019	Tolvaptan activated Nrf2 and increased mRNA and protein expression of antioxidant enzyme heme oxygenase-1 (HO-1) in mpkCCD cells and the outer medulla of mouse kidneys.	Tolvaptan	0-9	heme oxygenase 1	Mus musculus	89-105
31239473-6	2019	Tolvaptan activated Nrf2 and increased mRNA and protein expression of antioxidant enzyme heme oxygenase-1 (HO-1) in mpkCCD cells and the outer medulla of mouse kidneys.	Tolvaptan	0-9	heme oxygenase 1	Mus musculus	107-111
31239473-8	2019	Tolvaptan activated the Nrf2/HO-1 antioxidant pathway through phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK).	Tolvaptan	0-9	nuclear factor, erythroid derived 2, like 2	Mus musculus	24-28
31239473-8	2019	Tolvaptan activated the Nrf2/HO-1 antioxidant pathway through phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK).	Tolvaptan	0-9	heme oxygenase 1	Mus musculus	29-33
31239473-8	2019	Tolvaptan activated the Nrf2/HO-1 antioxidant pathway through phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK).	Tolvaptan	0-9	eukaryotic translation initiation factor 2 alpha kinase 3	Mus musculus	81-133
31239473-8	2019	Tolvaptan activated the Nrf2/HO-1 antioxidant pathway through phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase (PERK).	Tolvaptan	0-9	eukaryotic translation initiation factor 2 alpha kinase 3	Mus musculus	135-139
31239473-9	2019	As a result, tolvaptan and BARD could successfully generate synergistic activating effects on Nrf2/HO-1 antioxidant pathway, suggesting that this combination therapy can contribute to the treatment of CKD.	Tolvaptan	13-22	nuclear factor, erythroid derived 2, like 2	Mus musculus	94-98
31239473-9	2019	As a result, tolvaptan and BARD could successfully generate synergistic activating effects on Nrf2/HO-1 antioxidant pathway, suggesting that this combination therapy can contribute to the treatment of CKD.	Tolvaptan	13-22	heme oxygenase 1	Mus musculus	99-103
30578153-0	2019	Determinants of Urine Volume in ADPKD Patients Using the Vasopressin V2 Receptor Antagonist Tolvaptan.	Tolvaptan	92-101	arginine vasopressin receptor 2	Homo sapiens	57-80
30703371-6	2019	What"s more, tolvaptan increased the expression of ZO-1 and occludin (p &lt; 0.05, vs vehicle), which might be attributed to the down-regulated effects of tolvaptan on MMP-9.	Tolvaptan	155-164	matrix metallopeptidase 9	Rattus norvegicus	168-173
31039325-5	2019	Tolvaptan, a vasopressin antagonist has been shown to slow disease progression and preserve renal function.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	13-24
31019162-1	2019	Administration of the selective arginine vasopressin V2 receptor antagonist tolvaptan to cirrhotic patients is controversial.	Tolvaptan	76-85	arginine vasopressin receptor 2	Homo sapiens	41-64
30801659-0	2019	Novel molecular mechanisms in the inhibition of adrenal aldosterone synthesis: Action of tolvaptan via vasopressin V2 receptor-independent pathway.	Tolvaptan	89-98	arginine vasopressin receptor 2	Homo sapiens	103-126
30801659-1	2019	BACKGROUND AND PURPOSE: We investigated the inhibitory effect and associated molecular mechanisms of tolvaptan on angiotensin II (AngII)-induced aldosterone production in vitro and in vivo.	Tolvaptan	101-110	angiotensinogen	Homo sapiens	114-128
30801659-1	2019	BACKGROUND AND PURPOSE: We investigated the inhibitory effect and associated molecular mechanisms of tolvaptan on angiotensin II (AngII)-induced aldosterone production in vitro and in vivo.	Tolvaptan	101-110	angiotensinogen	Homo sapiens	130-135
30801659-4	2019	KEY RESULTS: Tolvaptan suppressed AngII-induced aldosterone production in a dose-dependent manner in H295R cells, whereas neither AVP nor dDAVP in the presence or absence of AngII altered aldosterone production, suggesting the vasopressin V2 receptor was not involved in the inhibitory effect of tolvaptan on aldosterone synthesis.	Tolvaptan	13-22	angiotensinogen	Homo sapiens	34-39
30801659-5	2019	In addition, tolvaptan inhibited the AngII-induced increase in aldosterone synthase (CYP11B2) protein levels without suppressing CYP11B2 mRNA expression.	Tolvaptan	13-22	angiotensinogen	Homo sapiens	37-42
30801659-5	2019	In addition, tolvaptan inhibited the AngII-induced increase in aldosterone synthase (CYP11B2) protein levels without suppressing CYP11B2 mRNA expression.	Tolvaptan	13-22	cytochrome P450 family 11 subfamily B member 2	Homo sapiens	63-83
30801659-5	2019	In addition, tolvaptan inhibited the AngII-induced increase in aldosterone synthase (CYP11B2) protein levels without suppressing CYP11B2 mRNA expression.	Tolvaptan	13-22	cytochrome P450 family 11 subfamily B member 2	Homo sapiens	85-92
30801659-6	2019	Notably, tolvaptan increased the levels of unfolded protein response (UPR) marker DDIT3 and eIF2alpha phosphorylation (a UPR-induced event), which could block the translation of CYP11B2 mRNA into protein and thereby inhibit aldosterone production.	Tolvaptan	9-18	DNA damage inducible transcript 3	Homo sapiens	82-87
30801659-6	2019	Notably, tolvaptan increased the levels of unfolded protein response (UPR) marker DDIT3 and eIF2alpha phosphorylation (a UPR-induced event), which could block the translation of CYP11B2 mRNA into protein and thereby inhibit aldosterone production.	Tolvaptan	9-18	eukaryotic translation initiation factor 2A	Homo sapiens	92-101
30801659-6	2019	Notably, tolvaptan increased the levels of unfolded protein response (UPR) marker DDIT3 and eIF2alpha phosphorylation (a UPR-induced event), which could block the translation of CYP11B2 mRNA into protein and thereby inhibit aldosterone production.	Tolvaptan	9-18	cytochrome P450 family 11 subfamily B member 2	Homo sapiens	178-185
30801659-7	2019	In vivo, tolvaptan significantly inhibited AngII-induced increases in serum and adrenal aldosterone levels and CYP11B2 protein levels.	Tolvaptan	9-18	angiotensinogen	Homo sapiens	43-48
31410325-8	2019	She received two doses of tolvaptan 15mg and developed worsening in her total bilirubin (T Bili) and alkaline phosphatase (Alk Phos) levels.	Tolvaptan	26-35	ALK receptor tyrosine kinase	Homo sapiens	123-126
30801659-7	2019	In vivo, tolvaptan significantly inhibited AngII-induced increases in serum and adrenal aldosterone levels and CYP11B2 protein levels.	Tolvaptan	9-18	cytochrome P450 family 11 subfamily B member 2	Homo sapiens	111-118
30801659-9	2019	CONCLUSIONS AND IMPLICATIONS: Tolvaptan inhibited AngII-stimulated aldosterone production via a V2 receptor-independent pathway, which can counteract or even surpass its potential activating effect of diuresis-induced aldosterone secretion in certain aldosterone-mediated pathological conditions.	Tolvaptan	30-39	angiotensinogen	Homo sapiens	50-55
30637666-8	2019	Therefore, tolvaptan was initiated, which corrected his hyponatremia, and the patient was discharged.In summary, tolvaptan results in stable correction of hyponatremia in patients with terminal small-cell lung cancer complicated by the syndrome of inappropriate secretion of antidiuretic hormone.	Tolvaptan	113-122	arginine vasopressin	Homo sapiens	275-295
30426292-0	2019	Hydrochlorothiazide ameliorates polyuria caused by tolvaptan treatment of polycystic kidney disease in PCK rats.	Tolvaptan	51-60	phosphoenolpyruvate carboxykinase 1	Rattus norvegicus	103-106
30426292-8	2019	Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group.	Tolvaptan	93-102	aquaporin 2	Rattus norvegicus	9-20
30426292-8	2019	Notably, aquaporin 2 redistribution from the apical to intracellular domains was observed in tolvaptan-treated rats and was partially reversed in the tolvaptan + HCTZ group.	Tolvaptan	150-159	aquaporin 2	Rattus norvegicus	9-20
30802995-4	2019	More recently, a significant amount of research has been dedicated to the use of vasopressin antagonists, specifically tolvaptan, as adjunctive therapy to loop and thiazide diuretics.	Tolvaptan	119-128	arginine vasopressin	Homo sapiens	81-92
30774351-4	2019	Tolvaptan, a vasopressin antagonist, could be adopted in heart failure therapy as it reduces pre- and afterload by decreasing systolic blood pressure and blood volume.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	13-24
30665496-6	2019	In cultured cardiac fibroblasts, combined treatment with homocysteine and NaCl increased profibrotic and matrix gene expression and activation of PI3/Akt pathway; all these effects were attenuated by tolvaptan Vasopressin levels, gene expression and V2 receptor expression were increased in vivo and in vitro on exposure to profibrotic stimuli, and tolvaptan attenuated these in vivo and in vitro effects.	Tolvaptan	200-209	WAP four-disulfide core domain 15B	Rattus norvegicus	146-149
30665496-6	2019	In cultured cardiac fibroblasts, combined treatment with homocysteine and NaCl increased profibrotic and matrix gene expression and activation of PI3/Akt pathway; all these effects were attenuated by tolvaptan Vasopressin levels, gene expression and V2 receptor expression were increased in vivo and in vitro on exposure to profibrotic stimuli, and tolvaptan attenuated these in vivo and in vitro effects.	Tolvaptan	200-209	AKT serine/threonine kinase 1	Rattus norvegicus	150-153
30665496-6	2019	In cultured cardiac fibroblasts, combined treatment with homocysteine and NaCl increased profibrotic and matrix gene expression and activation of PI3/Akt pathway; all these effects were attenuated by tolvaptan Vasopressin levels, gene expression and V2 receptor expression were increased in vivo and in vitro on exposure to profibrotic stimuli, and tolvaptan attenuated these in vivo and in vitro effects.	Tolvaptan	200-209	arginine vasopressin	Rattus norvegicus	210-221
30689194-1	2019	Tolvaptan [Jynarque  (USA); Jinarc  (EU, Canada); Samsca  (Japan)] is a highly selective vasopressin V2 receptor antagonist approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	89-112
30873020-0	2019	Evidence for Effective Multiple K+-Current Inhibitions by Tolvaptan, a Non-peptide Antagonist of Vasopressin V2 Receptor.	Tolvaptan	58-67	arginine vasopressin receptor 2	Rattus norvegicus	97-120
30873020-1	2019	Tolvaptan (TLV), an oral non-peptide antagonist of vasopressin V2 receptor, has been increasingly used for managements in patients with hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	51-74
30873020-1	2019	Tolvaptan (TLV), an oral non-peptide antagonist of vasopressin V2 receptor, has been increasingly used for managements in patients with hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion.	Tolvaptan	11-14	arginine vasopressin receptor 2	Homo sapiens	51-74
30873020-5	2019	TLV at a concentration greater than 10 muM also suppressed the amplitude of erg-mediated K+ current or the activity of large-conductance Ca2+-activated K+ channels; however, this compound failed to alter the amplitude of hyperpolarization-activated cation current in GH3 cells.	Tolvaptan	0-3	ETS transcription factor ERG	Rattus norvegicus	76-79
30210135-5	2019	TLV is thought to function via vasopressin V2 receptor antagonism.	Tolvaptan	0-3	arginine vasopressin receptor 2	Homo sapiens	31-54
30504136-1	2019	Tolvaptan, a vasopressin V2-receptor antagonist, has demonstrated efficacy in slowing kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD).	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	13-36
30733892-3	2019	We report a case of Bortezomib-induced SIADH, in whom the use of tolvaptan, a vasopressin receptor-2 antagonist, permitted the continuation of triple combination anti-MM therapy with lenalidomide, Bortezomib and dexamethasone (RVD) in a female with aggressive disease, without the development of hyponatremia.	Tolvaptan	65-74	arginine vasopressin	Homo sapiens	78-89
30284699-1	2019	BACKGROUND AND OBJECTIVE: Tolvaptan, an oral vasopressin V2 receptor antagonist, has been widely used for the treatment of patients with cirrhosis and ascites.	Tolvaptan	26-35	arginine vasopressin receptor 2	Homo sapiens	45-68
30625470-2	2019	Tolvaptan is a non-peptide orally available arginine vasopressin V2 receptor antagonist.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	53-76
30036087-9	2019	AQP-2 protein expression was also upregulated, but was significantly inhibited by the adenyl cyclase inhibitor MDL12330A or the PKA inhibitor H89, but not the vasopressin 2 receptor (V2R) antagonist tolvaptan.	Tolvaptan	199-208	aquaporin 2	Mus musculus	0-5
30242840-15	2019	Our findings have mechanistic implications on the emerging use of vasopressin V2 receptor antagonists such as tolvaptan as safe and effective therapy for polycystic kidney disease and reveal a potential new regulator of transepithelial salt and water transport in the kidney.	Tolvaptan	110-119	arginine vasopressin receptor 2	Homo sapiens	66-89
30312449-2	2019	Tolvaptan is an orally available vasopressin V2 receptor antagonist.	Tolvaptan	0-9	arginine vasopressin receptor 2	Homo sapiens	33-56
30803403-7	2019	In the subgroup with preserved renal function at admission (eGFR &gt;= 30 ml/min/1.73 m2), the continuous use of tolvaptan increased composite events (aHR = 2.130, p = 0.02549).	Tolvaptan	113-122	epidermal growth factor receptor	Homo sapiens	60-64
30567514-11	2018	During treatment with tolvaptan SST levels remained stable 38.2 (23.8-70.7) pg/mL vs. 39.8 (31.2-58.5) pg/mL, p = 0.85), whereas SST levels decreased significantly during treatment with lanreotide (42.5 (33.2-55.0) pg/ml vs. 29.3 (24.8-37.6), p = 0.008).	Tolvaptan	22-31	somatostatin	Homo sapiens	32-35
33693073-6	2018	Although there was no difference in serum creatinine or eGFR in the 7 days between the 2 groups, serum cystatin C significantly decreased on day 7 in the tolvaptan group compared with the furosemide group.	Tolvaptan	154-163	cystatin C	Homo sapiens	103-113
30344205-4	2018	Moreover, we demonstrated that PTX3 had the crucial role for cardiac remodeling under pressure overload using two different genotypes of mice: PTX3 systemic knockout mice and transgenic mice with cardiac-specific overexpression of PTX3.Diuretics are the essential drug for HF treatment, and we designed multicenter, randomized study for evaluating the efficacy and safety of tolvaptan compared to carperitide.	Tolvaptan	375-384	pentraxin related gene	Mus musculus	31-35
31315326-1	2018	Background: Tolvaptan is an orally administered, nonpeptide, selective arginine vasopressin V(2) receptor antagonist that increases free water clearance, thereby correcting and increasing the low serum sodium levels in patients of cirrhosis, where hyponatremai is am major encountered problem.	Tolvaptan	12-21	arginine vasopressin receptor 2	Homo sapiens	80-105
30563565-1	2018	BACKGROUND: The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites.	Tolvaptan	51-60	arginine vasopressin receptor 2	Homo sapiens	16-39
30203914-8	2018	Treatment with tolvaptan attenuated CIH-induced atrial fibrosis, reduced AF inducibility, expression levels of miR-21 and its downstream factors were also improved.	Tolvaptan	15-24	microRNA 21	Rattus norvegicus	111-117
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	microRNA 21	Rattus norvegicus	53-59
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	sprouty RTK signaling antagonist 1	Rattus norvegicus	60-65
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	Eph receptor B1	Rattus norvegicus	66-69
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	matrix metallopeptidase 9	Rattus norvegicus	70-75
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	microRNA 21	Rattus norvegicus	77-83
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	phosphatase and tensin homolog	Rattus norvegicus	84-88
30203914-10	2018	These changes may be explained due to alterations in miR-21/Spry1/ERK/MMP-9, miR-21/PTEN/PI3K/AKT, and NF-kappaB pathways by tolvaptan.	Tolvaptan	125-134	AKT serine/threonine kinase 1	Rattus norvegicus	94-97
30147354-2	2018	The efficacy of tolvaptan, a vasopressin V2-receptor antagonist and aquaretic, has not been evaluated for fluid control in CKD with reduced renal function.	Tolvaptan	16-25	arginine vasopressin receptor 2	Homo sapiens	29-52
30364227-6	2018	We also report our experience using tolvaptan, a vasopressin receptor antagonist, in this patient to effectively maintain eunatremia.	Tolvaptan	36-45	arginine vasopressin	Homo sapiens	49-60
30303493-1	2018	Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors.	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	44-55
29629516-0	2018	Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone.	Tolvaptan	23-32	arginine vasopressin	Homo sapiens	110-130
30026287-9	2018	Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment.	Tolvaptan	48-57	epidermal growth factor receptor	Homo sapiens	11-15
30026287-10	2018	CONCLUSIONS: Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.	Tolvaptan	153-162	epidermal growth factor receptor	Homo sapiens	115-119
30026287-10	2018	CONCLUSIONS: Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.	Tolvaptan	153-162	epidermal growth factor receptor	Homo sapiens	218-222
29801549-0	2018	Tolvaptan for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone: Is the Dose Too High?	Tolvaptan	0-9	arginine vasopressin	Homo sapiens	57-77
29970015-1	2018	BACKGROUND: Currently, the vasopressin V2 receptor antagonist tolvaptan is the only available treatment for autosomal dominant polycystic kidney disease (ADPKD), but there are tolerability issues due to aquaretic side-effects such as polyuria.	Tolvaptan	62-71	arginine vasopressin receptor 2	Homo sapiens	27-50
29970015-5	2018	While using tolvaptan, rate of eGFR decline was - 1.35 mL/min/1.73m2 per year, whereas after hydrochlorothiazide was initiated this was - 3.97 mL/minute/1.73m2 per year.	Tolvaptan	12-21	epidermal growth factor receptor	Homo sapiens	31-35
29970015-6	2018	CONCLUSIONS: This case report indicates that while addition of hydrochlorothiazide may improve tolerability of vasopressin V2 receptor antagonists, co-prescription should only be used with great scrutiny as it may decrease tolvaptan effect on rate of ADPKD disease progression.	Tolvaptan	223-232	arginine vasopressin receptor 2	Homo sapiens	111-134
29751971-12	2018	Finally, the renal resistance of transgenic mice to FGF23 was partly overcome by tolvaptan.	Tolvaptan	81-90	fibroblast growth factor 23	Mus musculus	52-57
29467353-2	2018	BACKGROUND: Oral administration of tolvaptan, a vasopressin V2receptor antagonist, significantly reduces deterioration of renal function, which has recently been highlighted as an exacerbating factor for adverse events in patients with acute heart failure.	Tolvaptan	35-44	arginine vasopressin receptor 2	Homo sapiens	48-70
29128962-11	2018	Responders of tolvaptan have lower BUN and renin activity at baseline, and shorten hospitalization period.	Tolvaptan	14-23	renin	Homo sapiens	43-48
28455745-5	2018	The vasopressin V2 receptor (V2R) antagonist tolvaptan lowers cAMP in cystic tissues and slows renal cystic progression and kidney function decline when given over 3 years in adult ADPKD patients.	Tolvaptan	45-54	arginine vasopressin receptor 2	Homo sapiens	4-27
28379536-1	2018	Background: In TEMPO 3:4, the vasopressin V2 receptor antagonist tolvaptan slowed total kidney volume (TKV) growth and estimated glomerular filtration rate (eGFR) decline relative to placebo.	Tolvaptan	65-74	arginine vasopressin receptor 2	Homo sapiens	30-53
28455745-5	2018	The vasopressin V2 receptor (V2R) antagonist tolvaptan lowers cAMP in cystic tissues and slows renal cystic progression and kidney function decline when given over 3 years in adult ADPKD patients.	Tolvaptan	45-54	arginine vasopressin receptor 2	Homo sapiens	29-32
28984014-0	2018	Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis.	Tolvaptan	110-119	C-reactive protein	Homo sapiens	16-34
28984014-0	2018	Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis.	Tolvaptan	110-119	aquaporin 2	Homo sapiens	57-68
28984014-10	2018	On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis.	Tolvaptan	167-170	C-reactive protein	Homo sapiens	30-48
28984014-10	2018	On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis.	Tolvaptan	167-170	aquaporin 2	Homo sapiens	139-143