PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 8341294-1 1993 L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 50-78 8341294-1 1993 L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 80-84 8477410-0 1993 The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 14-43 8477410-1 1993 We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Levodopa 164-172 catechol-O-methyltransferase Homo sapiens 47-75 8477410-1 1993 We studied the effect of inhibiting the enzyme catechol-O-methyltransferase (COMT) by a novel COMT inhibitor, entacapone, on the pharmacokinetics and metabolism of levodopa in 12 healthy male volunteers. Levodopa 164-172 catechol-O-methyltransferase Homo sapiens 77-81 1584187-9 1992 Clinical trials are planned with levodopa pro-drugs and inhibitors of catechol-O-methyltransferase to learn if these approaches can improve problems of long-term levodopa therapy. Levodopa 162-170 catechol-O-methyltransferase Homo sapiens 70-98 8112370-3 1993 A small decrease in the AUC of homovanillic acid (HVA), the COMT dependent metabolite of levodopa, was observed (from 455 to 303 h.ng.ml-1). Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 60-64 1884738-11 1991 New COMT inhibitors may provide a valuable approach to the treatment of Parkinson"s disease in combination with L-dopa and dopa decarboxylase inhibitor therapy. Levodopa 112-118 catechol-O-methyltransferase Homo sapiens 4-8 1734304-7 1992 In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD. Levodopa 71-79 catechol-O-methyltransferase Homo sapiens 13-17 1958292-2 1991 The inhibition of dopa decarboxylase and monoamine oxidase B resulting from this combination suggests that there may be a counter-regulatory increase in the activity of the third main enzyme in the catabolism of levodopa, i.e. catecholamine-O-methyl transferase (COMT). Levodopa 212-220 catechol-O-methyltransferase Homo sapiens 227-261 1958292-2 1991 The inhibition of dopa decarboxylase and monoamine oxidase B resulting from this combination suggests that there may be a counter-regulatory increase in the activity of the third main enzyme in the catabolism of levodopa, i.e. catecholamine-O-methyl transferase (COMT). Levodopa 212-220 catechol-O-methyltransferase Homo sapiens 263-267 1958292-3 1991 The current study on 36 patients with Parkinson"s disease under long-term treatment with levodopa/dopadecarboxylase inhibitor showed, however, that the erythrocyte-COMT was unaffected by additional (-)-deprenyl medication. Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 164-168 1875781-2 1991 The mean soluble COMT activities with 3,4-dihydroxybenzoic acid (DBA) and 3,4-dihydroxyphenylalanine (L-DOPA) as substrate were 70-242 and 70-174 pmol/min mg, respectively. Levodopa 102-108 catechol-O-methyltransferase Homo sapiens 17-21 1875781-5 1991 The affinity of the soluble COMT was approximately 20 times higher for DBA (Km 15-19 microM) than for L-DOPA (Km 300-600 microM). Levodopa 102-108 catechol-O-methyltransferase Homo sapiens 28-32 1875781-6 1991 The Km-values for L-DOPA of AADC and COMT were of the same order of magnitude. Levodopa 18-24 catechol-O-methyltransferase Homo sapiens 37-41 2272023-0 1990 Effect of a novel catechol-O-methyltransferase inhibitor, nitecapone, on the metabolism of L-dopa in healthy volunteers. Levodopa 91-97 catechol-O-methyltransferase Homo sapiens 18-46 2289048-0 1990 L-dopa as substrate for human duodenal catechol-O-methyltransferase and aromatic L-amino acid decarboxylase. Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 39-67 2272023-11 1990 The changes in L-Dopa metabolism by COMT inhibitor warrant further clinical studies in Parkinson"s disease. Levodopa 15-21 catechol-O-methyltransferase Homo sapiens 36-40 34935105-7 2022 By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Levodopa 36-44 catechol-O-methyltransferase Homo sapiens 14-18 34962574-3 2022 Objective: To compare the long-term effects on patient-rated quality of life of adding a dopamine agonist vs a dopamine reuptake inhibitor (DRI), either a monoamine oxidase type B (MAO-B) inhibitor or a catechol-O-methyltransferase (COMT) inhibitor, to levodopa therapy for the treatment of patients with motor complications of PD. Levodopa 253-261 catechol-O-methyltransferase Homo sapiens 203-231 34962574-3 2022 Objective: To compare the long-term effects on patient-rated quality of life of adding a dopamine agonist vs a dopamine reuptake inhibitor (DRI), either a monoamine oxidase type B (MAO-B) inhibitor or a catechol-O-methyltransferase (COMT) inhibitor, to levodopa therapy for the treatment of patients with motor complications of PD. Levodopa 253-261 catechol-O-methyltransferase Homo sapiens 233-237 34346015-0 2021 Association of COMT rs4680 and MAO-B rs1799836 polymorphisms with levodopa-induced dyskinesia in Parkinson"s disease-a meta-analysis. Levodopa 66-74 catechol-O-methyltransferase Homo sapiens 15-19 34346015-3 2021 Thus, we performed a meta-analysis to assess whether COMT and MAO-B genetic variants are associated with an increased incidence of levodopa-induced dyskinesia (LID) in PD patients. Levodopa 131-139 catechol-O-methyltransferase Homo sapiens 53-57 34525893-3 2021 In contrast, only relatively recently have catechol-O-methyltransferase (COMT) inhibitors been utilized to block the other major pathway of degradation and optimize levodopa delivery to the brain. Levodopa 165-173 catechol-O-methyltransferase Homo sapiens 43-71 34630283-2 2021 The current levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced PD. Levodopa 12-20 catechol-O-methyltransferase Homo sapiens 77-106 34630283-2 2021 The current levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced PD. Levodopa 12-20 catechol-O-methyltransferase Homo sapiens 108-112 34225162-2 2021 COMT inhibitors enhance the bioavailability of levodopa to the brain, and therefore are combined with levodopa for the treatment of motor fluctuations in PD. Levodopa 47-55 catechol-O-methyltransferase Homo sapiens 0-4 34525893-3 2021 In contrast, only relatively recently have catechol-O-methyltransferase (COMT) inhibitors been utilized to block the other major pathway of degradation and optimize levodopa delivery to the brain. Levodopa 165-173 catechol-O-methyltransferase Homo sapiens 73-77 35563817-1 2022 The catechol-O-methyltransferase inhibitors entacapone and opicapone prolong the efficacy of conventional oral levodopa/dopa decarboxylase inhibitor formulations through an increase in levodopa plasma bioavailability. Levodopa 185-193 catechol-O-methyltransferase Homo sapiens 4-32 35603896-0 2022 Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson"s Disease: A Meta-Analysis and Systematic Review. Levodopa 73-81 catechol-O-methyltransferase Homo sapiens 15-43 35563817-2 2022 Catechol-O-methyltransferase inhibitors influence the homocysteine metabolism associated with levodopa/dopa decarboxylase application. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 0-28 35217995-3 2022 Catechol-O-methyl transferase inhibitors (COMT-Is) are one of the recommended first-line levodopa add-on therapies for the amelioration of end-of dose motor fluctuations in patient with advanced Parkinson"s disease. Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 42-46 32108308-2 2021 However, due to extensive peripheral metabolism by aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT), only a fraction of the levodopa dose reaches the brain unchanged. Levodopa 151-159 catechol-O-methyltransferase Homo sapiens 91-119 35180134-1 2022 BACKGROUND: Long-term levodopa administration for treating Parkinson"s disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy. Levodopa 22-30 catechol-O-methyltransferase Homo sapiens 164-192 35180134-1 2022 BACKGROUND: Long-term levodopa administration for treating Parkinson"s disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy. Levodopa 22-30 catechol-O-methyltransferase Homo sapiens 194-198 6437857-4 1984 To reduce peaks and rapid fluctuations of L-DOPA plasma levels (possibly responsible for peak-dose dyskinesias and end-of-dose deterioration) a slow-release formulation of L-DOPA in combination with benserazide or with benserazide plus catechol-O-methyltransferase inhibitors should be developed. Levodopa 172-178 catechol-O-methyltransferase Homo sapiens 236-264 6734032-3 1984 Since Caucasians with Parkinson"s disease who had high RBC-COMT activity appeared to have more adverse effects from levodopa (L-dopa) than had those with low RBC-COMT activity, L-dopa doses and adverse responses in Filipinos with parkinsonism were compared to those of Caucasians with parkinsonism. Levodopa 116-124 catechol-O-methyltransferase Homo sapiens 59-63 6734032-5 1984 The possible association of the clinical differences in L-dopa tolerance and response between Filipinos and Caucasians with Parkinson"s disease, with the racial differences in RBC-COMT activity is discussed. Levodopa 56-62 catechol-O-methyltransferase Homo sapiens 180-184 6714437-5 1984 The genetically controlled level of COMT activity in the RBC reflects the level of enzyme activity in other tissues and is significantly correlated with individual variations in the methyl conjugation of catechol drugs such as L-dopa and methyldopa. Levodopa 227-233 catechol-O-methyltransferase Homo sapiens 36-40 7137962-8 1982 The data presented here indicate that use of catechol-O-methyltransferase inhibitors with L-dopa may be of value in the treatment of parkinsonian patients. Levodopa 90-96 catechol-O-methyltransferase Homo sapiens 45-73 7121609-7 1982 U-0521, a potent COMT inhibitor, enhances the availability and utilization of levodopa in the brain and may thus be helpful in future treatment of parkinsonian patients. Levodopa 78-86 catechol-O-methyltransferase Homo sapiens 17-21 7296879-0 1981 Determination of free and conjugated catecholamines and L-3,4-dihydroxyphenylalanine in plasma and urine: evidence for a catechol-O-methyltransferase inhibitor in uraemia. Levodopa 56-84 catechol-O-methyltransferase Homo sapiens 121-149 847319-5 1977 The authors express the view that abnormal movements while under L-Dopa treatment are dependent on two factors: one, the hypersensitivity of dopaminergic reception, the other, the greater or lesser preponderance of the COMT isozyme giving rise to 4-O-methylates; Levodopa 65-71 catechol-O-methyltransferase Homo sapiens 219-223 34007239-3 2021 Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for end-of-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Levodopa 100-106 catechol-O-methyltransferase Homo sapiens 0-29 34007239-3 2021 Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for end-of-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Levodopa 100-106 catechol-O-methyltransferase Homo sapiens 31-35 34007239-3 2021 Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for end-of-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Levodopa 169-175 catechol-O-methyltransferase Homo sapiens 0-29 34007239-3 2021 Catechol-O-methyl transferase (COMT) inhibitors (COMT-i) are used as first-line adjuvant therapy to L-dopa for end-of-dose (EoD) motor fluctuations, since they increase L-dopa availability in the brain by inhibiting its peripheral metabolism. Levodopa 169-175 catechol-O-methyltransferase Homo sapiens 31-35 7398195-0 1980 Catechol-O-methyltransferase activity: a determinant of levodopa response. Levodopa 56-64 catechol-O-methyltransferase Homo sapiens 0-28 7398195-1 1980 In 14 patients with Parkinson"s disease on long-term therapy the erythrocyte catechol-O-methyltransferase activity was found to correlate with the average plasma concentration ratio of 3-O-methyldopa to levodopa and with the fasting plasma concentration ratio of 3-O methyldopa to levodopa. Levodopa 203-211 catechol-O-methyltransferase Homo sapiens 77-105 7398195-1 1980 In 14 patients with Parkinson"s disease on long-term therapy the erythrocyte catechol-O-methyltransferase activity was found to correlate with the average plasma concentration ratio of 3-O-methyldopa to levodopa and with the fasting plasma concentration ratio of 3-O methyldopa to levodopa. Levodopa 281-289 catechol-O-methyltransferase Homo sapiens 77-105 7398195-2 1980 Patients with the higher erythrocyte catechol-O-methyltransferase activities were those with less favorable clinical responses to levodopa. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 37-65 7398195-3 1980 Since erythrocyte catechol-O-methyltransferase activity may reflect the activity of that enzyme in the major metabolizing tissues, catechol-O-methyltransferase activity would seem to be a significant determinant of response to levodopa. Levodopa 227-235 catechol-O-methyltransferase Homo sapiens 131-159 5016575-0 1972 Metabolism of L-dopa after inhibition of catechol-O-methyl transferase. Levodopa 14-20 catechol-O-methyltransferase Homo sapiens 41-70 5112212-0 1971 Potentiation of the L-Dopa effect in man by the use of catechol-O-methyltransferase inhibitors. Levodopa 20-26 catechol-O-methyltransferase Homo sapiens 55-83 32108308-2 2021 However, due to extensive peripheral metabolism by aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT), only a fraction of the levodopa dose reaches the brain unchanged. Levodopa 151-159 catechol-O-methyltransferase Homo sapiens 121-125 32108308-3 2021 Thus, by preventing levodopa metabolism and increasing the availability of levodopa for uptake into the brain, the inhibition of COMT would be beneficial in Parkinson"s disease. Levodopa 20-28 catechol-O-methyltransferase Homo sapiens 129-133 32108308-3 2021 Thus, by preventing levodopa metabolism and increasing the availability of levodopa for uptake into the brain, the inhibition of COMT would be beneficial in Parkinson"s disease. Levodopa 75-83 catechol-O-methyltransferase Homo sapiens 129-133 32588409-2 2020 MAO-B inhibitors are used as monotherapy as well as in combination with levodopa, whereas COMT inhibitors exert their effects only in conjungtion with levodopa. Levodopa 151-159 catechol-O-methyltransferase Homo sapiens 90-94 33136226-0 2021 Impact of the catechol-O-methyltransferase Val158Met polymorphism on the pharmacokinetics of L-dopa and its metabolite 3-O-methyldopa in combination with entacapone. Levodopa 93-99 catechol-O-methyltransferase Homo sapiens 14-42 33136226-2 2021 The effect of entacapone on the pharmacokinetics of L-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. Levodopa 52-58 catechol-O-methyltransferase Homo sapiens 132-160 33136226-2 2021 The effect of entacapone on the pharmacokinetics of L-dopa differs between patients with high-activity (H/H) and low-activity (L/L) catechol-O-methyltransferase (COMT) Val158Met polymorphisms, but the effects are unclear in heterozygous (H/L) patients. Levodopa 52-58 catechol-O-methyltransferase Homo sapiens 162-166 33136226-4 2021 Therefore, the present study aimed to clarify the effect of the COMT Val158Met polymorphism on the concentrations of L-dopa and 3-OMD in the presence of entacapone. Levodopa 117-123 catechol-O-methyltransferase Homo sapiens 64-68 33352833-1 2020 Entacapone, a reversible inhibitor of catechol-O-methyl transferase, is used for patients in Parkinson"s disease because it increases the bioavailability and effectiveness of levodopa. Levodopa 175-183 catechol-O-methyltransferase Homo sapiens 38-67 33151475-7 2020 Multivariate Cox regression analysis showed increased risk to LID development for both Levodopa Dose Equivalency (LED) (Hazard ratios (HR) = 1.001; 95% CI 1.00-1.01; p = 0.009) and individuals carrying the COMT L/L genotype (HR = 2.974; 95% CI 1.12-7.83; p = 0.010). Levodopa 87-95 catechol-O-methyltransferase Homo sapiens 206-210 33093598-2 2020 The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. Levodopa 77-85 catechol-O-methyltransferase Homo sapiens 302-330 33093598-2 2020 The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. Levodopa 77-85 catechol-O-methyltransferase Homo sapiens 332-336 33093598-8 2020 The individuals with higher DDC and COMT enzyme activity showed tendencies towards higher levodopa CL/F. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 36-40 32450711-1 2020 INTRODUCTION: Opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson"s disease (PD) associated with L-DOPA/L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Levodopa 177-183 catechol-O-methyltransferase Homo sapiens 52-80 32450711-1 2020 INTRODUCTION: Opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson"s disease (PD) associated with L-DOPA/L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Levodopa 177-183 catechol-O-methyltransferase Homo sapiens 82-86 32450711-1 2020 INTRODUCTION: Opicapone (OPC) is a well-established catechol-O-methyltransferase (COMT) inhibitor that is approved for the treatment of Parkinson"s disease (PD) associated with L-DOPA/L-amino acid decarboxylase inhibitor (DDI) therapy allowing for prolonged activity due to a more continuous supply of L-DOPA in the brain. Levodopa 302-308 catechol-O-methyltransferase Homo sapiens 82-86 33840171-0 2021 In silico discovery and evaluation of phytochemicals binding mechanism against human catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in Parkinson disease. Levodopa 143-149 catechol-O-methyltransferase Homo sapiens 85-113 33840171-2 2021 Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Levodopa 144-150 catechol-O-methyltransferase Homo sapiens 210-238 33840171-2 2021 Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Levodopa 144-150 catechol-O-methyltransferase Homo sapiens 240-244 33220276-9 2021 Opicapone potentiated the improvements in Parkinson s-like symptoms produced by levodopa/benserazide combinations with concomitant increase in plasma levodopa exposure, reduction of plasma 3-O-methyldopa levels and erythrocyte catechol-O-methyltransferase activity, results that were later demonstrated in 2 large Phase 3 studies in Parkinson s disease patients. Levodopa 80-88 catechol-O-methyltransferase Homo sapiens 227-255 32515486-4 2020 Opicapone is a recent and selective third-generation COMT inhibitor which achieves marked increase in the bioavailability of levodopa. Levodopa 125-133 catechol-O-methyltransferase Homo sapiens 53-57 32533012-0 2020 Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson"s disease. Levodopa 76-84 catechol-O-methyltransferase Homo sapiens 22-50 32533012-9 2020 Our primary results showed the possible association of SNPs other than the most common functional rs4680 in COMT with interindividual variance in the L-dopa daily dose and susceptibility to dyskinesia in Chinese patients, although this was an exploratory study based on a small sample size. Levodopa 150-156 catechol-O-methyltransferase Homo sapiens 108-112 29670409-8 2018 This inhibitor of peripheral catechol-O-methyltransferase supports continuous brain delivery of levodopa and, thus, the continuous dopaminergic stimulation concept. Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 29-57 31829066-4 2019 In addition mutations in genes other than the DOPA genes such as RGS4, NRG1, COMT, AKT1 and DTNBP1 (SET 2) have also been implicated in the pathogenesis of schizophrenia. Levodopa 46-50 catechol-O-methyltransferase Homo sapiens 77-81 31258092-2 2019 To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Levodopa 27-33 catechol-O-methyltransferase Homo sapiens 88-116 31258092-2 2019 To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Levodopa 27-33 catechol-O-methyltransferase Homo sapiens 118-122 31258092-2 2019 To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Levodopa 180-186 catechol-O-methyltransferase Homo sapiens 88-116 31258092-2 2019 To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Levodopa 180-186 catechol-O-methyltransferase Homo sapiens 118-122 29578580-0 2018 MAO-B and COMT Genetic Variations Associated With Levodopa Treatment Response in Patients With Parkinson"s Disease. Levodopa 50-58 catechol-O-methyltransferase Homo sapiens 10-14 29578580-3 2018 In our study we investigated the possible relation among selected single-nucleotide polymorphisms (SNPs) in the MAO-B (rs1799836) and COMT (rs4680) genes and the therapeutic response to levodopa (l-dopa). Levodopa 186-194 catechol-O-methyltransferase Homo sapiens 134-138 29578580-8 2018 We observed that patients carrying MAO-B (rs1799836) A and AA genotypes and COMT (rs4680) LL genotype suffered more frequently from levodopa-induced-dyskinesia. Levodopa 132-140 catechol-O-methyltransferase Homo sapiens 76-80 32238065-7 2020 Constraint of catechol-O-methyltransferase reduces homocysteine synthesis due to diminished consumption of methyl groups for levodopa turnover at least in the periphery. Levodopa 125-133 catechol-O-methyltransferase Homo sapiens 14-42 30290160-10 2018 Opicapone fills the unmet need for a compound with sustained COMT inhibition which will improve levodopa bioavailability in patients with Parkinson"s disease. Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 61-65 29345156-1 2018 INTRODUCTION: Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. Levodopa 150-158 catechol-O-methyltransferase Homo sapiens 101-105 29345156-1 2018 INTRODUCTION: Opicapone (OPC) is a novel, potent, reversible, and purely peripheral third-generation COMT inhibitor, which provides an enhancement in levodopa (L-Dopa) availability. Levodopa 160-166 catechol-O-methyltransferase Homo sapiens 101-105 29345156-10 2018 It significantly decreases COMT activity, with half-life of COMT inhibition in human erythrocytes of 61.6 h and increases systemic exposure to L-Dopa. Levodopa 143-149 catechol-O-methyltransferase Homo sapiens 27-31 29697034-3 2018 When AADC is inhibited, 3-Omethylation Catalysed by Catechol-O-Methyltransferase (COMT) becomes a dominant metabolic pathway for L-dopa, and COMT inhibitors may thus also be used as adjuncts to L-dopa in Parkinson"s disease. Levodopa 129-135 catechol-O-methyltransferase Homo sapiens 52-80 29697034-5 2018 MATERIALS & METHODS: Based on the roles of COMT and MAO in the metabolism of L-dopa and dopamine, the present study attempts to discover novel dual inhibitors of these enzymes. Levodopa 81-87 catechol-O-methyltransferase Homo sapiens 47-51 29697034-3 2018 When AADC is inhibited, 3-Omethylation Catalysed by Catechol-O-Methyltransferase (COMT) becomes a dominant metabolic pathway for L-dopa, and COMT inhibitors may thus also be used as adjuncts to L-dopa in Parkinson"s disease. Levodopa 129-135 catechol-O-methyltransferase Homo sapiens 82-86 29697034-3 2018 When AADC is inhibited, 3-Omethylation Catalysed by Catechol-O-Methyltransferase (COMT) becomes a dominant metabolic pathway for L-dopa, and COMT inhibitors may thus also be used as adjuncts to L-dopa in Parkinson"s disease. Levodopa 129-135 catechol-O-methyltransferase Homo sapiens 141-145 29697034-3 2018 When AADC is inhibited, 3-Omethylation Catalysed by Catechol-O-Methyltransferase (COMT) becomes a dominant metabolic pathway for L-dopa, and COMT inhibitors may thus also be used as adjuncts to L-dopa in Parkinson"s disease. Levodopa 194-200 catechol-O-methyltransferase Homo sapiens 52-80 29697034-3 2018 When AADC is inhibited, 3-Omethylation Catalysed by Catechol-O-Methyltransferase (COMT) becomes a dominant metabolic pathway for L-dopa, and COMT inhibitors may thus also be used as adjuncts to L-dopa in Parkinson"s disease. Levodopa 194-200 catechol-O-methyltransferase Homo sapiens 82-86 29697034-3 2018 When AADC is inhibited, 3-Omethylation Catalysed by Catechol-O-Methyltransferase (COMT) becomes a dominant metabolic pathway for L-dopa, and COMT inhibitors may thus also be used as adjuncts to L-dopa in Parkinson"s disease. Levodopa 194-200 catechol-O-methyltransferase Homo sapiens 141-145 30075828-0 2018 Polymorphisms of Catechol-O-Methyl Transferase (COMT) Gene in Vulnerability to Levodopa-Induced Dyskinesia. Levodopa 79-87 catechol-O-methyltransferase Homo sapiens 17-46 29614697-5 2018 Peripheral catechol-O-methyltransferase (COMT) inhibition improves the bioavailability of levodopa and results in a prolonged response. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 11-39 29614697-5 2018 Peripheral catechol-O-methyltransferase (COMT) inhibition improves the bioavailability of levodopa and results in a prolonged response. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 41-45 30075828-0 2018 Polymorphisms of Catechol-O-Methyl Transferase (COMT) Gene in Vulnerability to Levodopa-Induced Dyskinesia. Levodopa 79-87 catechol-O-methyltransferase Homo sapiens 48-52 28234566-5 2017 Catechol-O-methyltransferase (COMT) inhibitors attain this goal by decreasing L-dopa peripheral metabolism. Levodopa 78-84 catechol-O-methyltransferase Homo sapiens 0-28 27763682-10 2017 CONCLUSION: Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition. Levodopa 131-139 catechol-O-methyltransferase Homo sapiens 199-227 28580819-1 2017 INTRODUCTION: Opicapone is a third generation, highly potent and effective catechol O-methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Levodopa 180-186 catechol-O-methyltransferase Homo sapiens 75-103 28580819-1 2017 INTRODUCTION: Opicapone is a third generation, highly potent and effective catechol O-methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Levodopa 180-186 catechol-O-methyltransferase Homo sapiens 105-109 28315782-9 2017 Our results demonstrate that human COMT overexpression confers a heightened susceptibility to l-DOPA-induced dyskinesia and alters molecular and neurochemical responses in the lesioned striatum of mice. Levodopa 94-100 catechol-O-methyltransferase Homo sapiens 35-39 28234566-5 2017 Catechol-O-methyltransferase (COMT) inhibitors attain this goal by decreasing L-dopa peripheral metabolism. Levodopa 78-84 catechol-O-methyltransferase Homo sapiens 30-34 27685665-4 2016 These compounds represent a novel series of potent COMT inhibitors that might be further optimized to new drugs useful for the treatment of Parkinson"s disease, as adjuncts in levodopa based therapy, or for the treatment of schizophrenia. Levodopa 176-184 catechol-O-methyltransferase Homo sapiens 51-55 30566298-2 2017 Levodopa still remains the gold standard for the treatment of motor symptoms of PD in advanced stage, but dopamine agonists, monoamine oxidase B inhibitors and catechol-O-methyltransferase inhibitors have--also been developed to provide more continuous oral delivery of dopaminergic stimulation in order to prevent and improve levodopa-induced motor complications, including wearing off phenomenon and peak-dose dyskinesia. Levodopa 327-335 catechol-O-methyltransferase Homo sapiens 160-188 28027332-1 2017 Importance: Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Levodopa 139-147 catechol-O-methyltransferase Homo sapiens 12-40 28027332-1 2017 Importance: Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Levodopa 139-147 catechol-O-methyltransferase Homo sapiens 42-46 27456338-1 2016 BACKGROUND: We evaluated the effects of 3-O-methyldopa (3-OMD), a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of L-DOPA in striatal astrocytes. Levodopa 80-86 catechol-O-methyltransferase Homo sapiens 106-134 27653922-8 2016 Subsequent ANCOVA analysis revealed that COMT genotype interacted with sex and daily levodopa equivalent dose (LED) to influence executive function. Levodopa 85-93 catechol-O-methyltransferase Homo sapiens 41-45 27456338-1 2016 BACKGROUND: We evaluated the effects of 3-O-methyldopa (3-OMD), a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of L-DOPA in striatal astrocytes. Levodopa 80-86 catechol-O-methyltransferase Homo sapiens 136-140 27456338-1 2016 BACKGROUND: We evaluated the effects of 3-O-methyldopa (3-OMD), a metabolite of L-DOPA which is formed by catechol-O-methyltransferase (COMT), on the uptake, metabolism, and neuroprotective effects of L-DOPA in striatal astrocytes. Levodopa 201-207 catechol-O-methyltransferase Homo sapiens 136-140 27456338-8 2016 Since some amount of entacapone can cross the blood-brain barrier, this reagent may enhance L-DOPA transportation by inhibiting COMT and increase the astrocyte-mediated neuroprotective effects of L-DOPA on dopaminergic neurons. Levodopa 92-98 catechol-O-methyltransferase Homo sapiens 128-132 26295926-1 2015 Entacapone is an inhibitor of catechol-O-methyltransferase (COMT) and is being used to extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson"s disease. Levodopa 120-128 catechol-O-methyltransferase Homo sapiens 30-58 27129930-0 2016 Levodopa and neuropathy risk in patients with Parkinson disease: Effect of COMT inhibition. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 75-79 27163503-11 2016 It was concluded that OPC is a new COMT inhibitor that significantly decreased COMT activity and increased systemic exposure to levodopa in PD patients with motor fluctuations. Levodopa 128-136 catechol-O-methyltransferase Homo sapiens 35-39 27493964-1 2016 Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with Parkinson"s disease (PD) as a consequence of levodopa methylation via catechol-O-methyltransferase (COMT). Levodopa 49-57 catechol-O-methyltransferase Homo sapiens 150-178 27493964-1 2016 Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with Parkinson"s disease (PD) as a consequence of levodopa methylation via catechol-O-methyltransferase (COMT). Levodopa 125-133 catechol-O-methyltransferase Homo sapiens 150-178 27493964-2 2016 Results from previous studies that assessed the effect of COMT inhibitors on levodopa-induced hyperhomocysteinemia are conflicting. Levodopa 77-85 catechol-O-methyltransferase Homo sapiens 58-62 26293352-8 2016 Similarly, and particularly if a wearing-off symptom is present, COMT inhibitors smoothen and prolong the action of levodopa. Levodopa 116-124 catechol-O-methyltransferase Homo sapiens 65-69 26295926-1 2015 Entacapone is an inhibitor of catechol-O-methyltransferase (COMT) and is being used to extend the therapeutic effect of levodopa in patients with advanced and fluctuating Parkinson"s disease. Levodopa 120-128 catechol-O-methyltransferase Homo sapiens 60-64 24770794-8 2014 More continuous levodopa brain delivery and lower 3-O-methyldopa bioavailability caused a better motor response during catechol-O-methyltransferase inhibition. Levodopa 16-24 catechol-O-methyltransferase Homo sapiens 119-147 25409768-1 2015 BACKGROUND AND PURPOSE: Catechol-O-methyltransferase (COMT) is an important target in the levodopa treatment of Parkinson"s disease; however, the inhibitors available have problems, and not all patients benefit from their efficacy. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 24-52 25409768-1 2015 BACKGROUND AND PURPOSE: Catechol-O-methyltransferase (COMT) is an important target in the levodopa treatment of Parkinson"s disease; however, the inhibitors available have problems, and not all patients benefit from their efficacy. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 54-58 25559423-2 2015 This narrative review aims to discuss the role of COMT inhibitors on peripheral levodopa metabolism and continuous brain delivery of levodopa, and to describe their metabolic properties. Levodopa 80-88 catechol-O-methyltransferase Homo sapiens 50-54 25559423-2 2015 This narrative review aims to discuss the role of COMT inhibitors on peripheral levodopa metabolism and continuous brain delivery of levodopa, and to describe their metabolic properties. Levodopa 133-141 catechol-O-methyltransferase Homo sapiens 50-54 25559423-6 2015 More continuous plasma behaviour was observed after the combination of levodopa/DDI formulations with COMT inhibitors. Levodopa 71-79 catechol-O-methyltransferase Homo sapiens 102-106 25559423-8 2015 These findings favour the concept of chronic levodopa/DDI application with concomitant inhibition of COMT and monoamine oxidase, since deamination of dopamine via this enzyme also generates free radicals. Levodopa 45-53 catechol-O-methyltransferase Homo sapiens 101-105 25476691-6 2015 Novel enzyme inhibitors enhancing l-dopa efficacy and half-life are also still being developed, including a novel catechol-O-methyltransferase inhibitor with once-daily pharmacokinetics, and there are studies testing the effects of increasing the dose of amino acid decarboxylase inhibitors given concomitantly with l-dopa. Levodopa 34-40 catechol-O-methyltransferase Homo sapiens 114-142 24770794-0 2014 Fewer fluctuations, higher maximum concentration and better motor response of levodopa with catechol-O-methyltransferase inhibition. Levodopa 78-86 catechol-O-methyltransferase Homo sapiens 92-120 24770794-1 2014 Catechol-O-methyltransferase inhibitor addition to levodopa/carbidopa formulations improves motor symptoms and reduces levodopa fluctuations in patients with Parkinson"s disease. Levodopa 51-59 catechol-O-methyltransferase Homo sapiens 0-28 24770794-1 2014 Catechol-O-methyltransferase inhibitor addition to levodopa/carbidopa formulations improves motor symptoms and reduces levodopa fluctuations in patients with Parkinson"s disease. Levodopa 119-127 catechol-O-methyltransferase Homo sapiens 0-28 24770794-5 2014 Catechol-O-methyltransferase inhibition caused less fluctuations and higher baseline levels of levodopa after the first intake and less 3-O-methyldopa appearance. Levodopa 95-103 catechol-O-methyltransferase Homo sapiens 0-28 24770794-6 2014 The maximum levodopa concentrations were higher after the second levodopa intake, particularly with catechol-O-methyltransferase inhibition. Levodopa 12-20 catechol-O-methyltransferase Homo sapiens 100-128 24770794-6 2014 The maximum levodopa concentrations were higher after the second levodopa intake, particularly with catechol-O-methyltransferase inhibition. Levodopa 65-73 catechol-O-methyltransferase Homo sapiens 100-128 24770794-7 2014 The motor response to levodopa was better with catechol-O-methyltransferase inhibition than without, tolcapone was superior to entacapone. Levodopa 22-30 catechol-O-methyltransferase Homo sapiens 47-75 25510857-4 2015 RESULTS: The COMT 158val allele was associated with an increased startle potentiation by unpleasant stimuli as compared with neutral stimuli irrespective of L-dopa or placebo intervention. Levodopa 157-163 catechol-O-methyltransferase Homo sapiens 13-17 25510857-5 2015 COMT 158met/met genotype carriers, while displaying no difference in startle magnitude in response to unpleasant or neutral pictures in the placebo condition, showed startle potentiation by unpleasant pictures under L-dopa administration only. Levodopa 216-222 catechol-O-methyltransferase Homo sapiens 0-4 25510857-6 2015 CONCLUSIONS: The present proof-of-concept study provides preliminary support for a complex, multilevel impact of the dopaminergic system on the emotion-potentiated startle reflex suggesting increased phasic dopamine transmission driven by the more active COMT 158val allele and/or a single dose of L-dopa to predispose to maladaptive emotional processing and thereby potentially also to anxiety-related psychopathological states. Levodopa 298-304 catechol-O-methyltransferase Homo sapiens 255-259 25649051-1 2015 BACKGROUND AND PURPOSE: Opicapone (OPC) is a novel third generation catechol-O-methyltransferase (COMT) inhibitor that enhances levodopa availability. Levodopa 128-136 catechol-O-methyltransferase Homo sapiens 68-96 25649051-1 2015 BACKGROUND AND PURPOSE: Opicapone (OPC) is a novel third generation catechol-O-methyltransferase (COMT) inhibitor that enhances levodopa availability. Levodopa 128-136 catechol-O-methyltransferase Homo sapiens 98-102 25649051-11 2015 CONCLUSIONS: OPC is a promising new COMT inhibitor that significantly decreased COMT activity, increased systemic exposure to levodopa and improved motor response. Levodopa 126-134 catechol-O-methyltransferase Homo sapiens 36-40 25154960-1 2014 BACKGROUND: Levodopa (l-dopa) therapy in Parkinson"s disease (PD) increases serum homocysteine levels because of its metabolism via catechol O-methyltransferase, which may lead to endothelial dysfunction. Levodopa 12-20 catechol-O-methyltransferase Homo sapiens 132-160 25154960-1 2014 BACKGROUND: Levodopa (l-dopa) therapy in Parkinson"s disease (PD) increases serum homocysteine levels because of its metabolism via catechol O-methyltransferase, which may lead to endothelial dysfunction. Levodopa 22-28 catechol-O-methyltransferase Homo sapiens 132-160 24148813-11 2014 Opicapone is a strong candidate to fill the unmet need for COMT inhibitors that lead to more sustained levodopa levels in Parkinson"s disease patients. Levodopa 103-111 catechol-O-methyltransferase Homo sapiens 59-63 24925090-2 2014 The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone. Levodopa 45-53 catechol-O-methyltransferase Homo sapiens 109-113 24271646-1 2014 PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson"s disease. Levodopa 118-126 catechol-O-methyltransferase Homo sapiens 66-70 24716406-1 2014 Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson"s disease through boosting the concentration of dopamine in the brain. Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 0-28 24716406-1 2014 Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson"s disease through boosting the concentration of dopamine in the brain. Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 30-34 24716406-1 2014 Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson"s disease through boosting the concentration of dopamine in the brain. Levodopa 99-105 catechol-O-methyltransferase Homo sapiens 0-28 24716406-1 2014 Catechol O-methyltransferase (COMT) is an important enzyme involved in the metabolism of levodopa (L-dopa) which is clinically used to treat Parkinson"s disease through boosting the concentration of dopamine in the brain. Levodopa 99-105 catechol-O-methyltransferase Homo sapiens 30-34 24925090-15 2014 CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. Levodopa 150-158 catechol-O-methyltransferase Homo sapiens 48-52 24925090-15 2014 CONCLUSION: Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. Levodopa 150-158 catechol-O-methyltransferase Homo sapiens 218-222 24830331-2 2014 Entacapone, a peripheral inhibitor of catechol-O-methyltransferase (COMT), reduces this motor complication by prolonging the effect of levodopa. Levodopa 135-143 catechol-O-methyltransferase Homo sapiens 38-66 24830331-2 2014 Entacapone, a peripheral inhibitor of catechol-O-methyltransferase (COMT), reduces this motor complication by prolonging the effect of levodopa. Levodopa 135-143 catechol-O-methyltransferase Homo sapiens 68-72 24716406-2 2014 Development of COMT inhibitors can efficiently increase the bioavailability of L-dopa. Levodopa 79-85 catechol-O-methyltransferase Homo sapiens 15-19 24008922-8 2014 The possibility that combined COMT and MAO-A genotype is a significant factor in determining an individual"s lifetime levodopa exposure warrants further investigation. Levodopa 118-126 catechol-O-methyltransferase Homo sapiens 30-34 23206800-5 2013 While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. Levodopa 130-136 catechol-O-methyltransferase Homo sapiens 68-96 24532988-4 2013 In the review pharmacogenetic aspects of levodopa, dopamine agonists and COMT inhibitors are discussed. Levodopa 41-49 catechol-O-methyltransferase Homo sapiens 73-77 24234932-0 2013 Association Between Catechol-O-Methyltransferase (COMT) Gene Polymorphisms, Parkinson"s Disease, and Levodopa Efficacy. Levodopa 101-109 catechol-O-methyltransferase Homo sapiens 20-48 24234932-0 2013 Association Between Catechol-O-Methyltransferase (COMT) Gene Polymorphisms, Parkinson"s Disease, and Levodopa Efficacy. Levodopa 101-109 catechol-O-methyltransferase Homo sapiens 50-54 24234932-1 2013 OBJECTIVES: We investigated the association between catechol-O-methyltransferase (COMT) gene polymorphisms and Parkinson"s disease (PD) susceptibility, severity of disease, and levodopa (L-Dopa) efficacy. Levodopa 177-185 catechol-O-methyltransferase Homo sapiens 52-80 23237479-9 2013 CONCLUSIONS: In line with the model of non-linear effects of l-dopa on cortical plasticity high dopaminergic prefrontal activity mediated by COMT Val158Met polymorphism predicts a detrimental effect of anodal tDCS on cognitive flexibility. Levodopa 61-67 catechol-O-methyltransferase Homo sapiens 141-145 23206800-5 2013 While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. Levodopa 130-136 catechol-O-methyltransferase Homo sapiens 98-102 23206800-5 2013 While both tea catechins and quercetin strongly inhibit human liver catechol-O-methyltransferase (COMT)-mediated O-methylation of L-DOPA in vitro, only (+)-catechin exerts a significant inhibition of L-DOPA methylation in both peripheral compartment and striatum in rats. Levodopa 200-206 catechol-O-methyltransferase Homo sapiens 98-102 23948989-3 2013 Entacapone, a catechol-O-methyltransferase inhibitor, can also be used to improve the bioavailability of levodopa, especially when used in conjunction with a DDCI. Levodopa 105-113 catechol-O-methyltransferase Homo sapiens 14-42 22123108-1 2012 In the past years, it has been recognised that the levodopa therapy may be improved with therapeutic regimens including a catechol-O-methyltransferase (COMT) inhibitor. Levodopa 51-59 catechol-O-methyltransferase Homo sapiens 122-150 23020119-5 2012 Two major peripheral L-Dopa metabolic pathways, driven by the enzymes Aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyl transferase (COMT), significantly deplete the amount of L-Dopa reaching the brain. Levodopa 21-27 catechol-O-methyltransferase Homo sapiens 117-146 23020119-5 2012 Two major peripheral L-Dopa metabolic pathways, driven by the enzymes Aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyl transferase (COMT), significantly deplete the amount of L-Dopa reaching the brain. Levodopa 21-27 catechol-O-methyltransferase Homo sapiens 148-152 23020119-5 2012 Two major peripheral L-Dopa metabolic pathways, driven by the enzymes Aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyl transferase (COMT), significantly deplete the amount of L-Dopa reaching the brain. Levodopa 191-197 catechol-O-methyltransferase Homo sapiens 117-146 23020119-5 2012 Two major peripheral L-Dopa metabolic pathways, driven by the enzymes Aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyl transferase (COMT), significantly deplete the amount of L-Dopa reaching the brain. Levodopa 191-197 catechol-O-methyltransferase Homo sapiens 148-152 23994933-2 2013 The aim of the study was to verify whether a combination of levodopa with DOPA decarboxylase and catechol-O-methyltransferase inhibitors (stalevo) could delay the development of dyskinesia compared to the standard two-component drug due to the more stable concentration levodopa in the blood that provided the persistent stimulation of dopamine receptors in the striatum. Levodopa 270-278 catechol-O-methyltransferase Homo sapiens 97-125 22136069-0 2012 Intestinal levodopa infusion and COMT inhibition - a promising link. Levodopa 11-19 catechol-O-methyltransferase Homo sapiens 33-37 22136163-1 2012 BACKGROUND AND PURPOSE: Catechol-O-methyltransferase inhibitors may be used to decrease levodopa requirement. Levodopa 88-96 catechol-O-methyltransferase Homo sapiens 24-52 22136163-2 2012 The objective was to investigate whether the levodopa/carbidopa intestinal gel infusion dose can be reduced by 20% without worsening of motor fluctuations and levodopa concentration stability when oral catechol-O-methyltransferase inhibitors are added. Levodopa 45-53 catechol-O-methyltransferase Homo sapiens 202-230 22136163-10 2012 CONCLUSIONS: According to this small, short-term pilot study, oral catechol-O-methyltransferase inhibitors administered in 5-h intervals may be useful in cases where levodopa/carbidopa intestinal gel dose reduction is wanted. Levodopa 166-174 catechol-O-methyltransferase Homo sapiens 67-95 22483291-0 2012 Role of catechol-O-methyltransferase (COMT)-dependent processes in Parkinson"s disease and L-DOPA treatment. Levodopa 91-97 catechol-O-methyltransferase Homo sapiens 8-36 22483291-0 2012 Role of catechol-O-methyltransferase (COMT)-dependent processes in Parkinson"s disease and L-DOPA treatment. Levodopa 91-97 catechol-O-methyltransferase Homo sapiens 38-42 22483291-3 2012 There are several mechanisms for the potential involvement of COMT-related processes in the pathophysiology of Parkinson"s disease or the consequences of L-DOPA treatment. Levodopa 154-160 catechol-O-methyltransferase Homo sapiens 62-66 22483291-4 2012 COMT-mediated metabolism of LDOPA in the periphery influences brain dopamine levels, while the product of central COMT-mediated dopamine metabolism, 3-methoxytyramine, can affect movement via interaction with Trace Amine-Associated Receptor 1 (TAAR1). Levodopa 28-33 catechol-O-methyltransferase Homo sapiens 0-4 22123108-1 2012 In the past years, it has been recognised that the levodopa therapy may be improved with therapeutic regimens including a catechol-O-methyltransferase (COMT) inhibitor. Levodopa 51-59 catechol-O-methyltransferase Homo sapiens 152-156 22093536-4 2011 Dopamine agonists, catechol-O-methyltransferase inhibitors and monoamine oxidase-B inhibitors are anti-parkinsonian (anti-PD) drugs that have been found to further improve the potency of l-dopa and prevent the onset of motor complications. Levodopa 187-193 catechol-O-methyltransferase Homo sapiens 19-47 23093014-3 2012 Herein, we aimed to test the possible influence of MAOB and COMT genetic polymorphisms on the effective daily dose of levodopa administered in the fifth year of treatment. Levodopa 118-126 catechol-O-methyltransferase Homo sapiens 60-64 23093014-13 2012 The present data suggest that pharmacokinetic or pharmacodynamic factors other than the investigated genetic variants of the MAOB and COMT enzymes seem to determine the response to levodopa in the Iranian PD patients. Levodopa 181-189 catechol-O-methyltransferase Homo sapiens 134-138 22863920-1 2012 It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson"s disease (PD) patients receiving long term L-DOPA therapy. Levodopa 70-98 catechol-O-methyltransferase Homo sapiens 118-146 22863920-1 2012 It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson"s disease (PD) patients receiving long term L-DOPA therapy. Levodopa 70-98 catechol-O-methyltransferase Homo sapiens 148-152 22863920-1 2012 It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson"s disease (PD) patients receiving long term L-DOPA therapy. Levodopa 100-106 catechol-O-methyltransferase Homo sapiens 118-146 22863920-1 2012 It has been well known that 3-O-methyldopa (3-OMD) is a metabolite of L-3,4-dihydroxyphenylalanine (L-DOPA) formed by catechol O-methyltransferase (COMT), and 3-OMD blood level often reaches higher than physiological level in Parkinson"s disease (PD) patients receiving long term L-DOPA therapy. Levodopa 100-106 catechol-O-methyltransferase Homo sapiens 148-152 20464572-1 2010 Peripheral metabolism of L-DOPA via enzyme catechol-O-methyltransferase (COMT) is one of the possible sources of homocysteine (HCY). Levodopa 25-31 catechol-O-methyltransferase Homo sapiens 43-71 22053701-5 2011 We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. Levodopa 63-71 catechol-O-methyltransferase Homo sapiens 15-19 22053701-5 2011 We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 15-19 21533995-0 2011 Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson"s disease. Levodopa 92-100 catechol-O-methyltransferase Homo sapiens 14-42 21533995-2 2011 Degradation of levodopa to 3-O-methyldopa via the enzyme catechol-O-methyltransferase (COMT) is a methyl group demanding reaction. Levodopa 15-23 catechol-O-methyltransferase Homo sapiens 57-85 21533995-2 2011 Degradation of levodopa to 3-O-methyldopa via the enzyme catechol-O-methyltransferase (COMT) is a methyl group demanding reaction. Levodopa 15-23 catechol-O-methyltransferase Homo sapiens 87-91 21533995-10 2011 Levodopa bioavailability was higher on day 2 due to the COMT inhibition. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 56-60 21538606-1 2011 L-Dopa, the standard therapeutic for Parkinson"s disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 87-115 21538606-1 2011 L-Dopa, the standard therapeutic for Parkinson"s disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 117-121 21538606-2 2011 COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. Levodopa 125-131 catechol-O-methyltransferase Homo sapiens 0-4 21280081-1 2011 OBJECTIVE: In Parkinson disease (PD), the selective C-O-methyltransferase (COMT) inhibitor entacapone prolongs the effect of levodopa on motor symptoms (ON time) by increasing its bioavailability. Levodopa 125-133 catechol-O-methyltransferase Homo sapiens 52-73 21280081-1 2011 OBJECTIVE: In Parkinson disease (PD), the selective C-O-methyltransferase (COMT) inhibitor entacapone prolongs the effect of levodopa on motor symptoms (ON time) by increasing its bioavailability. Levodopa 125-133 catechol-O-methyltransferase Homo sapiens 75-79 21280081-8 2011 Area under the concentration over time curve of levodopa increased more after entacapone in COMT(HH) than in COMT(LL) patients (+62 +- 6% vs +34 +- 8%, p = 0.01). Levodopa 48-56 catechol-O-methyltransferase Homo sapiens 92-96 21280081-8 2011 Area under the concentration over time curve of levodopa increased more after entacapone in COMT(HH) than in COMT(LL) patients (+62 +- 6% vs +34 +- 8%, p = 0.01). Levodopa 48-56 catechol-O-methyltransferase Homo sapiens 109-113 21280081-10 2011 INTERPRETATION: The COMT(HH) genotype in PD patients enhances the effect of entacapone on the pharmacodynamics and pharmacokinetics of levodopa. Levodopa 135-143 catechol-O-methyltransferase Homo sapiens 20-24 21164341-1 2011 OBJECTIVES: Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD). Levodopa 152-158 catechol-O-methyltransferase Homo sapiens 75-104 21164341-1 2011 OBJECTIVES: Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD). Levodopa 152-158 catechol-O-methyltransferase Homo sapiens 106-110 25205926-5 2011 Other pharmacological measures like catechol-O-methyltrasferase (COMT) inhibitors like entacopone, telcapone and monoamine oxidase B (MAO-B) inhibitors like selegiline and rasagiline are also useful, while L-dopa remains the gold standard in the treatment of PD. Levodopa 206-212 catechol-O-methyltransferase Homo sapiens 36-63 21738693-1 2011 BACKGROUND: Levodopa treatment in Parkinson"s disease (PD) increases in serum homocysteine levels due to its metabolism via catechol O-methyltransferase. Levodopa 12-20 catechol-O-methyltransferase Homo sapiens 124-152 20464572-1 2010 Peripheral metabolism of L-DOPA via enzyme catechol-O-methyltransferase (COMT) is one of the possible sources of homocysteine (HCY). Levodopa 25-31 catechol-O-methyltransferase Homo sapiens 73-77 20856911-5 2010 In recent years, a new, safe, and efficacious armamentarium of treatment options has been provided by the marketing of the catechol-O-methyltransferase (COMT) inhibitor, entacapone, a peripheral blocker of dopa to 3-0-methyldopa metabolism, which increments levodopa brain availability. Levodopa 258-266 catechol-O-methyltransferase Homo sapiens 123-151 20856911-5 2010 In recent years, a new, safe, and efficacious armamentarium of treatment options has been provided by the marketing of the catechol-O-methyltransferase (COMT) inhibitor, entacapone, a peripheral blocker of dopa to 3-0-methyldopa metabolism, which increments levodopa brain availability. Levodopa 258-266 catechol-O-methyltransferase Homo sapiens 153-157 20812452-1 2010 In Stalevo tablets, used in the therapy of patients with Parkinson"s disease, levodopa is combined with decarboxylase inhibitors and COMT inhibitors to provide a more steady plasma concentration of levodopa. Levodopa 198-206 catechol-O-methyltransferase Homo sapiens 133-137 20700524-2 2010 Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. Levodopa 136-142 catechol-O-methyltransferase Homo sapiens 45-49 20700524-5 2010 EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Levodopa 67-73 catechol-O-methyltransferase Homo sapiens 36-40 19909787-7 2010 Our results also support the conclusion that COMT inhibitors (entacapone or tolcapone), when administered in PD patients treated with l-Dopa, may potentiate the endogenous AdoHcy-dependent COMT inhibition mechanism already operative in a variable fashion. Levodopa 134-140 catechol-O-methyltransferase Homo sapiens 45-49 19676096-4 2010 Therefore, the purpose of our study was to assess COMT activity in OCD by measuring plasma levels of 3-O-methyl-dopa (3-OMD), which result from the methylation of levodopa by COMT, and to investigate the relationship between 3-OMD levels and the V158M polymorphism. Levodopa 163-171 catechol-O-methyltransferase Homo sapiens 50-54 20582993-2 2010 It has been hypothesized that providing more continuous delivery of L-dopa to the brain would reduce the risk of motor complications, and that this might be accomplished by combining L-dopa with entacapone, an inhibitor of catechol-O-methyltransferase, to extend its elimination half-life. Levodopa 183-189 catechol-O-methyltransferase Homo sapiens 223-251 20077469-1 2010 Levodopa combined with a dopa-decarboxylase inhibitor, such as carbidopa, shifts the metabolism to the COMT pathway. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 103-107 19879254-12 2010 Thus, COMT inhibitors are useful for decreasing the amount of levodopa administered to Parkinson"s disease patients. Levodopa 62-70 catechol-O-methyltransferase Homo sapiens 6-10 21095456-0 2010 Introductory remarks: Catechol-O-methyltransferase inhibition--an innovative approach to enhance L-dopa therapy in Parkinson"s disease with dual enzyme inhibition. Levodopa 97-103 catechol-O-methyltransferase Homo sapiens 22-50 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 195-203 catechol-O-methyltransferase Homo sapiens 0-28 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 195-203 catechol-O-methyltransferase Homo sapiens 30-34 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 195-203 catechol-O-methyltransferase Homo sapiens 322-326 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 205-211 catechol-O-methyltransferase Homo sapiens 0-28 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 205-211 catechol-O-methyltransferase Homo sapiens 30-34 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 205-211 catechol-O-methyltransferase Homo sapiens 322-326 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 222-228 catechol-O-methyltransferase Homo sapiens 0-28 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 222-228 catechol-O-methyltransferase Homo sapiens 30-34 21095456-1 2010 Catechol-O-methyltransferase (COMT) enzyme and its inhibition have been closely related to the treatment of Parkinson"s disease (PD) patients with motor fluctuations needing enhancement of their levodopa (L-dopa) therapy (L-dopa/dopa decarboxylase inhibitor), this indication being so far the only clinical application of COMT inhibitors. Levodopa 222-228 catechol-O-methyltransferase Homo sapiens 322-326 21095456-3 2010 The introduction of clinically effective and safe COMT inhibitors has greatly increased the usefulness of L-dopa therapy, but how to utilize the full potential of L-dopa is still unsolved leaving a need for more potent COMT inhibitors. Levodopa 106-112 catechol-O-methyltransferase Homo sapiens 50-54 21095459-2 2010 Homocysteine decrease may therefore be a future therapeutic challenge, which may be achieved by supplementation with certain vitamins or by combination of a catechol-O-methyltransferase (COMT) inhibitor with L-dopa/DDI administration. Levodopa 208-214 catechol-O-methyltransferase Homo sapiens 187-191 21095461-3 2010 One approach to provide a more continuous and sustained delivery of dopamine has targeted one of the principal enzymes responsible for metabolic deactivation of L-dopa, namely catechol-O-methyltransferase (COMT). Levodopa 161-167 catechol-O-methyltransferase Homo sapiens 176-204 21095461-3 2010 One approach to provide a more continuous and sustained delivery of dopamine has targeted one of the principal enzymes responsible for metabolic deactivation of L-dopa, namely catechol-O-methyltransferase (COMT). Levodopa 161-167 catechol-O-methyltransferase Homo sapiens 206-210 21095462-1 2010 The development of catechol-O-methyltransferase (COMT) inhibitors for the adjunct treatment to levodopa and aromatic L-amino acid decarboxylase (AADC) inhibitors in Parkinson"s disease started in the late 1950s. Levodopa 95-103 catechol-O-methyltransferase Homo sapiens 19-47 21095462-1 2010 The development of catechol-O-methyltransferase (COMT) inhibitors for the adjunct treatment to levodopa and aromatic L-amino acid decarboxylase (AADC) inhibitors in Parkinson"s disease started in the late 1950s. Levodopa 95-103 catechol-O-methyltransferase Homo sapiens 49-53 21095464-9 2010 The most common adverse event with COMT inhibitors is dyskinesia which is usually managed by decreasing levodopa dose. Levodopa 104-112 catechol-O-methyltransferase Homo sapiens 35-39 19909787-7 2010 Our results also support the conclusion that COMT inhibitors (entacapone or tolcapone), when administered in PD patients treated with l-Dopa, may potentiate the endogenous AdoHcy-dependent COMT inhibition mechanism already operative in a variable fashion. Levodopa 134-140 catechol-O-methyltransferase Homo sapiens 189-193 19936145-4 2009 Recent LD trials indicate that a combination of LD with carbidopa (CD) and the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) may reduce the onset of these motor complications to a certain extent. Levodopa 7-9 catechol-O-methyltransferase Homo sapiens 79-107 19936145-4 2009 Recent LD trials indicate that a combination of LD with carbidopa (CD) and the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) may reduce the onset of these motor complications to a certain extent. Levodopa 7-9 catechol-O-methyltransferase Homo sapiens 109-113 19538218-5 2009 Levodopa efficacy and duration of effect may be enhanced by combination with a catechol-O-methyl transferase inhibitor. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 79-108 19922897-2 2009 Coadministration of a COMT inhibitor with levodopa and a dopa-decarboxylase inhibitor (carbidopa or benserazide) increases levodopa exposure and its therapeutic effect. Levodopa 42-50 catechol-O-methyltransferase Homo sapiens 22-26 19922897-2 2009 Coadministration of a COMT inhibitor with levodopa and a dopa-decarboxylase inhibitor (carbidopa or benserazide) increases levodopa exposure and its therapeutic effect. Levodopa 123-131 catechol-O-methyltransferase Homo sapiens 22-26 19657587-0 2009 Peripheral COMT inhibition prevents levodopa associated homocysteine increase. Levodopa 36-44 catechol-O-methyltransferase Homo sapiens 11-15 19167259-8 2009 CONCLUSION: The use of COMT or MAO-B inhibitors plus levodopa is superior to levodopa alone at reducing PD symptoms in patients with advanced PD. Levodopa 77-85 catechol-O-methyltransferase Homo sapiens 23-27 18510366-6 2008 Changing from mono- to bisubstrate inhibitors of catechol O-methyltransferase, a target in the L-Dopa-based treatment of Parkinson"s disease, enabled the full exploitation of a previously unexplored hydrophobic pocket. Levodopa 95-101 catechol-O-methyltransferase Homo sapiens 49-77 19798454-0 2009 Genetic polymorphism of catechol O-methyltransferase and pharmacokinetics of levodopa in healthy Chinese subjects. Levodopa 77-85 catechol-O-methyltransferase Homo sapiens 24-52 19056347-3 2009 The main clinical interest in COMT results from the possibility of using COMT inhibitors as adjuncts in the therapy of Parkinson"s disease (PD) with l-DOPA. Levodopa 149-155 catechol-O-methyltransferase Homo sapiens 30-34 19056347-3 2009 The main clinical interest in COMT results from the possibility of using COMT inhibitors as adjuncts in the therapy of Parkinson"s disease (PD) with l-DOPA. Levodopa 149-155 catechol-O-methyltransferase Homo sapiens 73-77 19131039-2 2009 The dose of l-dopa can be reduced by the combined administration of inhibitors of peripheral l-amino acid decarboxylase (AADC), catechol O-methyltransferase (COMT), or monoamine oxidase B (MAO B). Levodopa 12-18 catechol-O-methyltransferase Homo sapiens 158-162 19589043-6 2009 When levodopa is administered with a DDCI, its main route of peripheral metabolism is via catechol-O-methyl transferase (COMT). Levodopa 5-13 catechol-O-methyltransferase Homo sapiens 90-119 19589043-6 2009 When levodopa is administered with a DDCI, its main route of peripheral metabolism is via catechol-O-methyl transferase (COMT). Levodopa 5-13 catechol-O-methyltransferase Homo sapiens 121-125 19589043-7 2009 A COMT inhibitor can be added to the combination of levodopa and a DDCI to further extend the levodopa peripheral half-life and increase central bioavailability. Levodopa 52-60 catechol-O-methyltransferase Homo sapiens 2-6 19589043-7 2009 A COMT inhibitor can be added to the combination of levodopa and a DDCI to further extend the levodopa peripheral half-life and increase central bioavailability. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 2-6 19407449-3 2009 Current strategies include concomitant treatment with inhibitors of dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) to prolong the peripheral levodopa half-life and increase CNS bioavailability. Levodopa 159-167 catechol-O-methyltransferase Homo sapiens 97-125 19407449-3 2009 Current strategies include concomitant treatment with inhibitors of dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) to prolong the peripheral levodopa half-life and increase CNS bioavailability. Levodopa 159-167 catechol-O-methyltransferase Homo sapiens 127-131 19131039-2 2009 The dose of l-dopa can be reduced by the combined administration of inhibitors of peripheral l-amino acid decarboxylase (AADC), catechol O-methyltransferase (COMT), or monoamine oxidase B (MAO B). Levodopa 12-18 catechol-O-methyltransferase Homo sapiens 128-156 18698234-0 2008 The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson"s disease, levodopa treatment response, and complications. Levodopa 104-112 catechol-O-methyltransferase Homo sapiens 30-58 18698234-1 2008 INTRODUCTION: Differences in catechol-O-methyltransferase (COMT) activity and genotype may determine individual variations in the therapeutic response to levodopa or Parkinson"s disease (PD) susceptibility. Levodopa 154-162 catechol-O-methyltransferase Homo sapiens 29-57 18698234-1 2008 INTRODUCTION: Differences in catechol-O-methyltransferase (COMT) activity and genotype may determine individual variations in the therapeutic response to levodopa or Parkinson"s disease (PD) susceptibility. Levodopa 154-162 catechol-O-methyltransferase Homo sapiens 59-63 18698234-3 2008 OBJECTIVES: In this case-control study, we investigated the association of the most common COMT gene haplotypes (formed by single nucleotide polymorphisms (SNPs): rs6269:A>G; rs4633C>T; rs4818:C>G; and rs4680:A>G) with PD risk and the association of the COMT haplotypes with the dose and complications of levodopa therapy in PD patients. Levodopa 305-313 catechol-O-methyltransferase Homo sapiens 91-95 18698234-15 2008 The doses of levodopa treatment can be influenced by specific COMT haplotypes and this may be useful in instituting individualized therapy for PD patients. Levodopa 13-21 catechol-O-methyltransferase Homo sapiens 62-66 18290846-1 2008 Catechol-O-methyl transferase (COMT) inhibition by entacapone enhances levodopa absorption and reduces "off" time in Parkinson"s disease (PD). Levodopa 71-79 catechol-O-methyltransferase Homo sapiens 0-29 18520980-0 2008 Catechol-O-methyltransferase inhibition improves levodopa-associated strength increase in patients with Parkinson disease. Levodopa 49-57 catechol-O-methyltransferase Homo sapiens 0-28 18290846-1 2008 Catechol-O-methyl transferase (COMT) inhibition by entacapone enhances levodopa absorption and reduces "off" time in Parkinson"s disease (PD). Levodopa 71-79 catechol-O-methyltransferase Homo sapiens 31-35 18728767-1 2008 Levodopa is the most effective treatment in Parkinson"s disease and the association with COMT inhibitors widens its plasma bioavailability and effectiveness. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 89-93 18289028-6 2008 Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Levodopa 13-21 catechol-O-methyltransferase Homo sapiens 121-149 18289028-6 2008 Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Levodopa 13-21 catechol-O-methyltransferase Homo sapiens 151-155 18289028-6 2008 Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Levodopa 23-29 catechol-O-methyltransferase Homo sapiens 121-149 18289028-6 2008 Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Levodopa 23-29 catechol-O-methyltransferase Homo sapiens 151-155 18289028-6 2008 Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Levodopa 99-105 catechol-O-methyltransferase Homo sapiens 121-149 18289028-6 2008 Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Levodopa 99-105 catechol-O-methyltransferase Homo sapiens 151-155 18322402-1 2008 BACKGROUND: A significant percentage of patients with Parkinson"s disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors. Levodopa 186-194 catechol-O-methyltransferase Homo sapiens 200-204 18989992-13 2008 CONCLUSION: Following concomitant administration with levodopa/carbidopa CR 200 mg/50 mg, single doses of nebicapone 50 mg, 100 mg and 200 mg significantly and dose-dependently inhibited S-COMT activity, increased systemic exposure to levodopa, and reduced 3-OMD formation. Levodopa 54-62 catechol-O-methyltransferase Homo sapiens 189-193 17894650-4 2007 The last decade showed that the use of catechol-O-methyltransferase inhibitors as adjuvants to the levodopa/AADC inhibitor therapy, significantly improves the clinical benefits of this therapy. Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 39-67 18221241-3 2008 In fact, recent development efforts have been primarily directed at stabilizing the side effects (wearing off, drug-induced dyskinesias, motor fluctuations) that accompany prolonged levodopa therapy, such as catechol O-methyltransferase inhibiton to combat the side effects of levodopa therapy. Levodopa 182-190 catechol-O-methyltransferase Homo sapiens 208-236 18221241-3 2008 In fact, recent development efforts have been primarily directed at stabilizing the side effects (wearing off, drug-induced dyskinesias, motor fluctuations) that accompany prolonged levodopa therapy, such as catechol O-methyltransferase inhibiton to combat the side effects of levodopa therapy. Levodopa 277-285 catechol-O-methyltransferase Homo sapiens 208-236 17573159-11 2007 These changes in glial and perivascular catechol-O-methyltransferase activity may have clinical relevance for Parkinson"s disease drug treatment due to increased metabolism of levodopa in the brain. Levodopa 176-184 catechol-O-methyltransferase Homo sapiens 40-68 18052761-3 2007 Catechol-O-methyltransferase (COMT) is a selective and widely distributed enzyme involved in the catabolism of levodopa. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 0-28 18052761-3 2007 Catechol-O-methyltransferase (COMT) is a selective and widely distributed enzyme involved in the catabolism of levodopa. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 30-34 18052761-4 2007 Tolcapone and entacapone are selective and potent COMT inhibitors that slow the metabolism of levodopa, thus prolonging its effects. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 50-54 17936857-5 2007 Strategies that may improve the bioavailability of levodopa, the most efficacious medication for Parkinson"s disease, include coadministering levodopa with carbidopa, a decarboxylase inhibitor, or with a catechol-O-methyltransferase inhibitor or using an alternative route of administration. Levodopa 51-59 catechol-O-methyltransferase Homo sapiens 204-232 17894650-5 2007 The purpose of this article is to review the current knowledge on the enzyme catechol-O-methyltransferase (COMT) and the role of COMT inhibitors in PD as a new therapeutic approach to PD involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. Levodopa 211-219 catechol-O-methyltransferase Homo sapiens 77-105 17894650-5 2007 The purpose of this article is to review the current knowledge on the enzyme catechol-O-methyltransferase (COMT) and the role of COMT inhibitors in PD as a new therapeutic approach to PD involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. Levodopa 211-219 catechol-O-methyltransferase Homo sapiens 107-111 17894650-5 2007 The purpose of this article is to review the current knowledge on the enzyme catechol-O-methyltransferase (COMT) and the role of COMT inhibitors in PD as a new therapeutic approach to PD involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. Levodopa 211-219 catechol-O-methyltransferase Homo sapiens 129-133 17495756-6 2007 In addition, preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced may be associated with fewer motor complications than treatment with levodopa alone. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 68-96 17495756-6 2007 In addition, preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced may be associated with fewer motor complications than treatment with levodopa alone. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 98-102 17495756-6 2007 In addition, preclinical studies suggest that adjunctive use of the catechol-O-methyltransferase (COMT) inhibitor entacapone when levodopa is first introduced may be associated with fewer motor complications than treatment with levodopa alone. Levodopa 228-236 catechol-O-methyltransferase Homo sapiens 68-96 17630819-10 2007 Selegiline ODT is also absorbed more efficiently and shows less pharmacokinetic variability than conventional oral selegiline.COMT mediates peripheral catabolism of levodopa. Levodopa 165-173 catechol-O-methyltransferase Homo sapiens 126-130 17963454-3 2007 The mechanism underlying L-Dopa-related HHcy is the O-methylation of the drug catalyzed by the enzyme catechol-O-methyltransferase (COMT). Levodopa 25-31 catechol-O-methyltransferase Homo sapiens 102-130 17963454-3 2007 The mechanism underlying L-Dopa-related HHcy is the O-methylation of the drug catalyzed by the enzyme catechol-O-methyltransferase (COMT). Levodopa 25-31 catechol-O-methyltransferase Homo sapiens 132-136 17963454-6 2007 This review summarizes data available in the literature concerning the two main therapeutic approaches to L-Dopa-related HHcy (use of COMT inhibitors or B vitamins diet supplementation). Levodopa 106-112 catechol-O-methyltransferase Homo sapiens 134-138 17630819-11 2007 Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Levodopa 107-115 catechol-O-methyltransferase Homo sapiens 29-33 17630819-12 2007 Given adjunctively with levodopa, COMT inhibitors can decrease "off" time and increase "on" time, as well as lower the daily levodopa dose. Levodopa 24-32 catechol-O-methyltransferase Homo sapiens 34-38 17630819-12 2007 Given adjunctively with levodopa, COMT inhibitors can decrease "off" time and increase "on" time, as well as lower the daily levodopa dose. Levodopa 125-133 catechol-O-methyltransferase Homo sapiens 34-38 16989543-7 2006 Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa serum half-life and allow more levodopa to be delivered to the brain over a longer time, thereby smoothing dopaminergic stimulation. Levodopa 59-67 catechol-O-methyltransferase Homo sapiens 0-28 17702535-7 2007 Catechol-O-methyltransferase inhibitors may be used to augment levodopa in the setting of "wearing off" (i.e. motor fluctuations). Levodopa 63-71 catechol-O-methyltransferase Homo sapiens 0-28 17059382-2 2006 Tolcapone is a catechol-O-methyltransferase inhibitor that extends the action of levodopa. Levodopa 81-89 catechol-O-methyltransferase Homo sapiens 15-43 16604302-1 2006 Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Levodopa 108-116 catechol-O-methyltransferase Homo sapiens 16-44 16604302-1 2006 Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Levodopa 108-116 catechol-O-methyltransferase Homo sapiens 46-50 17948614-8 2006 Catechol-O-methyltransferase (COMT)inhibitors extend the half-life of levodopa and result in significant reductions in off times in patients with motor fluctuations. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 0-28 17948614-8 2006 Catechol-O-methyltransferase (COMT)inhibitors extend the half-life of levodopa and result in significant reductions in off times in patients with motor fluctuations. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 30-34 17948613-7 2006 Catechol-O-methyltransferase (COMT)inhibitors, which increase dopamine levels by inhibiting the metabolism of levodopa and dopamine, recently have become available, including a tablet containing carbidopa, levodopa,and entacapone. Levodopa 110-118 catechol-O-methyltransferase Homo sapiens 0-28 17948613-7 2006 Catechol-O-methyltransferase (COMT)inhibitors, which increase dopamine levels by inhibiting the metabolism of levodopa and dopamine, recently have become available, including a tablet containing carbidopa, levodopa,and entacapone. Levodopa 110-118 catechol-O-methyltransferase Homo sapiens 30-34 17948613-7 2006 Catechol-O-methyltransferase (COMT)inhibitors, which increase dopamine levels by inhibiting the metabolism of levodopa and dopamine, recently have become available, including a tablet containing carbidopa, levodopa,and entacapone. Levodopa 206-214 catechol-O-methyltransferase Homo sapiens 0-28 17948613-7 2006 Catechol-O-methyltransferase (COMT)inhibitors, which increase dopamine levels by inhibiting the metabolism of levodopa and dopamine, recently have become available, including a tablet containing carbidopa, levodopa,and entacapone. Levodopa 206-214 catechol-O-methyltransferase Homo sapiens 30-34 16989543-7 2006 Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa serum half-life and allow more levodopa to be delivered to the brain over a longer time, thereby smoothing dopaminergic stimulation. Levodopa 59-67 catechol-O-methyltransferase Homo sapiens 30-34 16989543-7 2006 Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa serum half-life and allow more levodopa to be delivered to the brain over a longer time, thereby smoothing dopaminergic stimulation. Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 0-28 16989543-7 2006 Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa serum half-life and allow more levodopa to be delivered to the brain over a longer time, thereby smoothing dopaminergic stimulation. Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 30-34 16758261-3 2006 A further therapeutic alternative is inhibition of catechol-O-methyltransfrase (COMT) on a regular basis, when levodopa/DDI treatment is performed. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 51-78 16758261-3 2006 A further therapeutic alternative is inhibition of catechol-O-methyltransfrase (COMT) on a regular basis, when levodopa/DDI treatment is performed. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 80-84 16772808-1 2006 Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 123-151 16772808-1 2006 Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 153-157 16772808-1 2006 Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 123-151 16772808-1 2006 Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 153-157 16772808-2 2006 Although inhibition of COMT should theoretically prevent or reduce levodopa-induced HHcy, results from several prospective studies are conflicting. Levodopa 67-75 catechol-O-methyltransferase Homo sapiens 23-27 16772808-3 2006 Our review of these studies suggests that the ability of COMT inhibition to reduce or prevent levodopa-induced HHcy in Parkinson disease patients may be attributed to differences in the vitamin status of the study participants. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 57-61 15614425-2 2005 Levodopa is metabolised via O-methylation by catechol-O-methyltransferase (COMT) using S-adenosyl-L-methionine (SAM) as the methyl donor, this leading to the subsequent formation of homocysteine. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 45-73 16340382-1 2005 Metabolism of levodopa via the enzyme catechol-O-methyltransferase requires S-adenosylmethionine (SAM) as a methyl donor. Levodopa 14-22 catechol-O-methyltransferase Homo sapiens 38-66 16211593-0 2006 Inhibition of catechol-O-methyltransferase contributes to more stable levodopa plasma levels. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 14-42 18046910-3 2006 COMT inhibitors slow down the rapid metabolism of levodopa, resulting in a more-sustained response to dopaminergic therapy. Levodopa 50-58 catechol-O-methyltransferase Homo sapiens 0-4 16222437-5 2005 It can, therefore, be suggested that the onset of dyskinesia may be prolonged if levodopa is administered in a more continuous manner by administering it as a combination of levodopa/DDCI and COMT inhibitor. Levodopa 81-89 catechol-O-methyltransferase Homo sapiens 192-196 15614425-2 2005 Levodopa is metabolised via O-methylation by catechol-O-methyltransferase (COMT) using S-adenosyl-L-methionine (SAM) as the methyl donor, this leading to the subsequent formation of homocysteine. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 75-79 15503197-4 2005 Catechol-O-methyltransferase (COMT) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce "off" time. Levodopa 97-105 catechol-O-methyltransferase Homo sapiens 0-28 15779086-5 2005 tHcy export from astrocytes was also induced by the COMT substrates levodopa (L-DOPA), dopamine and quercetin, and it was blocked by the COMT inhibitors tropolone and entacapone. Levodopa 68-76 catechol-O-methyltransferase Homo sapiens 52-56 15779086-5 2005 tHcy export from astrocytes was also induced by the COMT substrates levodopa (L-DOPA), dopamine and quercetin, and it was blocked by the COMT inhibitors tropolone and entacapone. Levodopa 78-84 catechol-O-methyltransferase Homo sapiens 52-56 15747357-1 2005 We explored the potential effect of catechol-O-methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson"s disease (PD). Levodopa 165-173 catechol-O-methyltransferase Homo sapiens 66-70 15878587-3 2005 Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. Levodopa 98-106 catechol-O-methyltransferase Homo sapiens 39-67 15878587-3 2005 Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. Levodopa 98-106 catechol-O-methyltransferase Homo sapiens 69-73 15878587-3 2005 Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. Levodopa 189-197 catechol-O-methyltransferase Homo sapiens 39-67 15878587-3 2005 Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. Levodopa 189-197 catechol-O-methyltransferase Homo sapiens 69-73 15878587-9 2005 We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 20-24 15907741-2 2005 Catechol-O-methyltransferase (COMT) inhibitors delay the breakdown of levodopa, which leads to an increase in levodopa bioavailability and more stable concentrations of plasma levodopa. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 0-28 15907741-2 2005 Catechol-O-methyltransferase (COMT) inhibitors delay the breakdown of levodopa, which leads to an increase in levodopa bioavailability and more stable concentrations of plasma levodopa. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 30-34 15907741-2 2005 Catechol-O-methyltransferase (COMT) inhibitors delay the breakdown of levodopa, which leads to an increase in levodopa bioavailability and more stable concentrations of plasma levodopa. Levodopa 110-118 catechol-O-methyltransferase Homo sapiens 0-28 15907741-2 2005 Catechol-O-methyltransferase (COMT) inhibitors delay the breakdown of levodopa, which leads to an increase in levodopa bioavailability and more stable concentrations of plasma levodopa. Levodopa 110-118 catechol-O-methyltransferase Homo sapiens 30-34 15907741-2 2005 Catechol-O-methyltransferase (COMT) inhibitors delay the breakdown of levodopa, which leads to an increase in levodopa bioavailability and more stable concentrations of plasma levodopa. Levodopa 110-118 catechol-O-methyltransferase Homo sapiens 0-28 15907741-2 2005 Catechol-O-methyltransferase (COMT) inhibitors delay the breakdown of levodopa, which leads to an increase in levodopa bioavailability and more stable concentrations of plasma levodopa. Levodopa 110-118 catechol-O-methyltransferase Homo sapiens 30-34 15907741-3 2005 The addition of a COMT inhibitor therefore combines the rapid onset of levodopa with prolonged efficacy, and theoretically provides a more continuous stimulation of dopamine receptors with reduced risk of motor complications. Levodopa 71-79 catechol-O-methyltransferase Homo sapiens 18-22 15907741-4 2005 Randomised, controlled trials have shown that in patients with PD who have motor fluctuations, the addition of the COMT-inhibitor entacapone results in an improvement in motor fluctuations, particularly of the "wearing-off" type, with about 1.0-1.7 h more on-time and less off-time per day, reduced required levodopa dose, modest improvement in motor and disability scores (mean total unified PD rating scale [UPDRS] scores of about 4.5), and in some but not all studies improvement of health-related quality of life [HRQOL] scores. Levodopa 308-316 catechol-O-methyltransferase Homo sapiens 115-119 15747357-1 2005 We explored the potential effect of catechol-O-methyltransferase (COMT) genetic polymorphism on the pharmacokinetics and pharmacodynamics of a standard oral dose of levodopa in patients with Parkinson"s disease (PD). Levodopa 165-173 catechol-O-methyltransferase Homo sapiens 36-64 15503197-4 2005 Catechol-O-methyltransferase (COMT) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce "off" time. Levodopa 97-105 catechol-O-methyltransferase Homo sapiens 30-34 15709899-2 2005 To minimise this problem, selective catechol-O-methyltransferase (COMT) inhibitors were developed in order to improve the poor pharmacokinetic profile of levodopa. Levodopa 154-162 catechol-O-methyltransferase Homo sapiens 36-64 15709899-2 2005 To minimise this problem, selective catechol-O-methyltransferase (COMT) inhibitors were developed in order to improve the poor pharmacokinetic profile of levodopa. Levodopa 154-162 catechol-O-methyltransferase Homo sapiens 66-70 15390046-3 2005 The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. Levodopa 60-68 catechol-O-methyltransferase Homo sapiens 82-110 15390046-3 2005 The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. Levodopa 60-68 catechol-O-methyltransferase Homo sapiens 112-116 15495118-0 2004 Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson"s disease. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 0-28 15495118-2 2004 The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile "off" phase. Levodopa 89-97 catechol-O-methyltransferase Homo sapiens 21-25 15495118-7 2004 SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson"s disease and long-term complications of levodopa therapy. Levodopa 215-223 catechol-O-methyltransferase Homo sapiens 61-65 15495119-0 2004 Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson"s disease. Levodopa 44-52 catechol-O-methyltransferase Homo sapiens 0-28 15495119-2 2004 The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile "off" phase. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 21-25 15495119-3 2004 OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson"s disease, already established on levodopa and suffering from motor complications. Levodopa 158-166 catechol-O-methyltransferase Homo sapiens 59-63 15495119-7 2004 SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson"s disease and long-term complications of levodopa therapy. Levodopa 204-212 catechol-O-methyltransferase Homo sapiens 61-65 15355491-3 2004 The aim of the study was to evaluate the effect of MAOB and COMT genetic polymorphism on effective daily dose of levodopa applied during the first 5 years of treatment, and to find out if a relationship exists between MAOB and COMT haplotypes and motor disturbances onset in PD patients treated with levodopa preparations. Levodopa 113-121 catechol-O-methyltransferase Homo sapiens 60-64 15355491-9 2004 However, the frequency of COMT(L/L) homozygotes was higher in the group treated with low doses of levodopa when compared with the second group. Levodopa 98-106 catechol-O-methyltransferase Homo sapiens 26-30 15355491-10 2004 MAOB and COMT AG-HH haplotype predominated in the group of females treated with high daily doses of levodopa when compared with AG-LL haplotype in the group of females treated with low daily doses of levodopa (<500 mg/24 h). Levodopa 100-108 catechol-O-methyltransferase Homo sapiens 9-13 15355491-11 2004 CONCLUSION: The results of the study suggest that patients with COMT(L/L) genotype and possibly MAOB genotype A may benefit from more efficient and safer levodopa therapy. Levodopa 154-162 catechol-O-methyltransferase Homo sapiens 64-68 15477510-1 2004 BACKGROUND: The catechol O-methyltransferase inhibitor entacapone acts by extending the elimination half-life of levodopa and is currently approved as an adjunct to levodopa for the treatment of patients with Parkinson disease (PD) with motor fluctuations. Levodopa 113-121 catechol-O-methyltransferase Homo sapiens 16-44 15477510-1 2004 BACKGROUND: The catechol O-methyltransferase inhibitor entacapone acts by extending the elimination half-life of levodopa and is currently approved as an adjunct to levodopa for the treatment of patients with Parkinson disease (PD) with motor fluctuations. Levodopa 165-173 catechol-O-methyltransferase Homo sapiens 16-44 15221622-1 2004 Entacapone is a specific, peripherally acting catechol- O-methyltransferase (COMT) inhibitor that prevents peripheral degradation of L-dopa, thus improving its bioavailability. Levodopa 133-139 catechol-O-methyltransferase Homo sapiens 46-75 15340869-1 2004 Two catechol- O-methyltransferase (COMT) inhibitors, entacapone and tolcapone, were developed during the 1990"s to be used as adjuncts to levodopa (LD) - dopa decarboxylase (DDC) inhibitors in the treatment of Parkinson"s disease (PD). Levodopa 138-146 catechol-O-methyltransferase Homo sapiens 4-33 15340869-1 2004 Two catechol- O-methyltransferase (COMT) inhibitors, entacapone and tolcapone, were developed during the 1990"s to be used as adjuncts to levodopa (LD) - dopa decarboxylase (DDC) inhibitors in the treatment of Parkinson"s disease (PD). Levodopa 138-146 catechol-O-methyltransferase Homo sapiens 35-39 15365141-4 2004 It has been suggested that breakdown of L-dopa by catechol-O-methyltransferase results in increased homocysteine formation. Levodopa 40-46 catechol-O-methyltransferase Homo sapiens 50-78 15379738-1 2004 BACKGROUND: Entacapone is a COMT inhibitor used in Parkinson"s disease (PD) patients, as an adjunctive therapy to L-dopa in order to prolong its bioavailability and thus its clinical effect. Levodopa 114-120 catechol-O-methyltransferase Homo sapiens 28-32 15221622-1 2004 Entacapone is a specific, peripherally acting catechol- O-methyltransferase (COMT) inhibitor that prevents peripheral degradation of L-dopa, thus improving its bioavailability. Levodopa 133-139 catechol-O-methyltransferase Homo sapiens 77-81 14975680-1 2004 Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used as adjuncts to levodopa in the treatment of Parkinson"s disease (PD). Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 29-57 15148140-1 2004 BACKGROUND: Levodopa metabolism via catechol O-methyltransferase increases levels of the neurotoxin homocysteine, which induces an axonal-accentuated degeneration in sensory peripheral nerves in vitro. Levodopa 12-20 catechol-O-methyltransferase Homo sapiens 36-64 15018791-1 2004 A simple and rapid assay is described for the simultaneous analysis of levodopa (l-DOPA) and 3-O-methyldopa (3-OMD) in human plasma samples, applying an ion-pair reversed-phase liquid chromatographic method with electrochemical detection, designed for clinical trials performed to study the effect of peripheral catechol-O-methyltransferase inhibitors on the metabolism of l-DOPA. Levodopa 81-87 catechol-O-methyltransferase Homo sapiens 312-340 14975680-1 2004 Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used as adjuncts to levodopa in the treatment of Parkinson"s disease (PD). Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 59-63 14767720-1 2004 The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinson"s disease (PD) patients. Levodopa 163-171 catechol-O-methyltransferase Homo sapiens 57-61 14718683-0 2004 COMT inhibitors in Parkinson"s disease: can they prevent and/or reverse levodopa-induced motor complications? Levodopa 72-80 catechol-O-methyltransferase Homo sapiens 0-4 12904105-1 2003 Entacapone and tolcapone are selective catechol-O-methyltransferase (COMT) inhibitors developed recently as adjuncts to levodopa for the treatment of Parkinson"s disease (PD). Levodopa 120-128 catechol-O-methyltransferase Homo sapiens 39-67 15354384-1 2004 Levodopa and dopamine are metabolized to 3-O-methyldopa and 3-methoxytyramine, respectively, by the enzyme catechol-O-methyltransferase (COMT) leading to the production of the demethylated cofactor S-adenosylhomo-cysteine (SAH) and subsequently homocysteine (HC). Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 107-135 15354384-1 2004 Levodopa and dopamine are metabolized to 3-O-methyldopa and 3-methoxytyramine, respectively, by the enzyme catechol-O-methyltransferase (COMT) leading to the production of the demethylated cofactor S-adenosylhomo-cysteine (SAH) and subsequently homocysteine (HC). Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 137-141 12898345-0 2003 L-DOPA biotransformation: correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 62-90 12898345-3 2003 Levels of activity for erythrocyte COMT were also reflected in individual variation in the metabolism of L-DOPA. Levodopa 105-111 catechol-O-methyltransferase Homo sapiens 35-39 12787259-7 2003 The novel COMT inhibitor BIA 3-202 is a potent COMT inhibitor that enhances the availability of L-DOPA to the brain by reducing its O-methylation, which may prove beneficial in patients with Parkinson"s disease treated with L-DOPA. Levodopa 96-102 catechol-O-methyltransferase Homo sapiens 10-14 12787259-7 2003 The novel COMT inhibitor BIA 3-202 is a potent COMT inhibitor that enhances the availability of L-DOPA to the brain by reducing its O-methylation, which may prove beneficial in patients with Parkinson"s disease treated with L-DOPA. Levodopa 96-102 catechol-O-methyltransferase Homo sapiens 47-51 12787259-7 2003 The novel COMT inhibitor BIA 3-202 is a potent COMT inhibitor that enhances the availability of L-DOPA to the brain by reducing its O-methylation, which may prove beneficial in patients with Parkinson"s disease treated with L-DOPA. Levodopa 224-230 catechol-O-methyltransferase Homo sapiens 10-14 12787259-7 2003 The novel COMT inhibitor BIA 3-202 is a potent COMT inhibitor that enhances the availability of L-DOPA to the brain by reducing its O-methylation, which may prove beneficial in patients with Parkinson"s disease treated with L-DOPA. Levodopa 224-230 catechol-O-methyltransferase Homo sapiens 47-51 15090932-0 2004 Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/carbidopa. Levodopa 91-99 catechol-O-methyltransferase Homo sapiens 71-75 15090932-15 2004 In conclusion, the novel COMT inhibitor BIA 3-202 increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard levodopa/carbidopa. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 25-29 15090932-15 2004 In conclusion, the novel COMT inhibitor BIA 3-202 increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard levodopa/carbidopa. Levodopa 159-167 catechol-O-methyltransferase Homo sapiens 25-29 14573393-1 2003 Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa metabolism. Levodopa 72-80 catechol-O-methyltransferase Homo sapiens 0-28 14573393-1 2003 Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa metabolism. Levodopa 72-80 catechol-O-methyltransferase Homo sapiens 30-34 14517707-0 2003 Pharmacokinetic-pharmacodynamic interaction between BIA 3-202, a novel COMT inhibitor, and levodopa/benserazide. Levodopa 91-99 catechol-O-methyltransferase Homo sapiens 71-75 14517707-1 2003 BIA 3-202 is a novel catechol-O-methyltransferase (COMT) inhibitor being developed for use as a levodopa-sparing agent in Parkinson"s disease. Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 21-49 14517707-1 2003 BIA 3-202 is a novel catechol-O-methyltransferase (COMT) inhibitor being developed for use as a levodopa-sparing agent in Parkinson"s disease. Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 51-55 14517707-12 2003 In conclusion, the novel COMT inhibitor BIA 3-202 was well tolerated and significantly increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard release levodopa/benserazide. Levodopa 120-128 catechol-O-methyltransferase Homo sapiens 25-29 14517707-12 2003 In conclusion, the novel COMT inhibitor BIA 3-202 was well tolerated and significantly increased the bioavailability of levodopa and reduced the formation of 3-OMD when administered with standard release levodopa/benserazide. Levodopa 204-212 catechol-O-methyltransferase Homo sapiens 25-29 12904105-1 2003 Entacapone and tolcapone are selective catechol-O-methyltransferase (COMT) inhibitors developed recently as adjuncts to levodopa for the treatment of Parkinson"s disease (PD). Levodopa 120-128 catechol-O-methyltransferase Homo sapiens 69-73 14593760-5 2003 The treatment of advanced stages of the disease currently requires the application of levodopa combined with other medicines, such as dopamine agonists or catechol-O-methyl transferase (COMT) inhibitors. Levodopa 86-94 catechol-O-methyltransferase Homo sapiens 155-184 14593760-5 2003 The treatment of advanced stages of the disease currently requires the application of levodopa combined with other medicines, such as dopamine agonists or catechol-O-methyl transferase (COMT) inhibitors. Levodopa 86-94 catechol-O-methyltransferase Homo sapiens 186-190 11899548-4 2002 The availability of several newer types of agents--dopamine agonists, monoamine oxidase inhibitors, and catechol-O-methyltransferase inhibitors--gives physicians increased flexibility with regard to first-line therapy, adjunct therapy, and managing or reducing the frequency of motor complications and other side effects associated with chronic levodopa therapy. Levodopa 345-353 catechol-O-methyltransferase Homo sapiens 104-132 14673217-1 2003 Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines, including levodopa. Levodopa 92-100 catechol-O-methyltransferase Homo sapiens 0-28 14673217-1 2003 Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines, including levodopa. Levodopa 92-100 catechol-O-methyltransferase Homo sapiens 30-34 12573867-11 2003 These primate studies have demonstrated that long-acting dopamine agonists and levodopa given in combination with a catechol-O-methyl transferase (COMT) inhibitor (to increase its relatively short half-life), induce significantly less dyskinesia than occurs with standard levodopa therapy. Levodopa 79-87 catechol-O-methyltransferase Homo sapiens 116-145 12573867-11 2003 These primate studies have demonstrated that long-acting dopamine agonists and levodopa given in combination with a catechol-O-methyl transferase (COMT) inhibitor (to increase its relatively short half-life), induce significantly less dyskinesia than occurs with standard levodopa therapy. Levodopa 79-87 catechol-O-methyltransferase Homo sapiens 147-151 12573867-11 2003 These primate studies have demonstrated that long-acting dopamine agonists and levodopa given in combination with a catechol-O-methyl transferase (COMT) inhibitor (to increase its relatively short half-life), induce significantly less dyskinesia than occurs with standard levodopa therapy. Levodopa 272-280 catechol-O-methyltransferase Homo sapiens 116-145 12573867-11 2003 These primate studies have demonstrated that long-acting dopamine agonists and levodopa given in combination with a catechol-O-methyl transferase (COMT) inhibitor (to increase its relatively short half-life), induce significantly less dyskinesia than occurs with standard levodopa therapy. Levodopa 272-280 catechol-O-methyltransferase Homo sapiens 147-151 12533089-3 2003 However, patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Levodopa 114-122 catechol-O-methyltransferase Homo sapiens 139-167 12908845-3 2003 Catechol-O-methyltransferase (COMT) inhibitors reduce levodopa metabolism and enhance the respective plasma levels, resulting in improvements in symptoms and overall quality of life. Levodopa 54-62 catechol-O-methyltransferase Homo sapiens 0-28 12908845-3 2003 Catechol-O-methyltransferase (COMT) inhibitors reduce levodopa metabolism and enhance the respective plasma levels, resulting in improvements in symptoms and overall quality of life. Levodopa 54-62 catechol-O-methyltransferase Homo sapiens 30-34 12236793-1 2002 BIA 3-202, 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenylethanone 3, is a novel, reversible, and tight-binding peripheral inhibitor of the enzyme catechol-O-methyltransferase (COMT), which is currently under clinical evaluation for the treatment of Parkinson"s disease as an adjunct to current L-Dopa/peripheral decarboxylase inhibitor therapy. Levodopa 288-294 catechol-O-methyltransferase Homo sapiens 140-168 12236793-1 2002 BIA 3-202, 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenylethanone 3, is a novel, reversible, and tight-binding peripheral inhibitor of the enzyme catechol-O-methyltransferase (COMT), which is currently under clinical evaluation for the treatment of Parkinson"s disease as an adjunct to current L-Dopa/peripheral decarboxylase inhibitor therapy. Levodopa 288-294 catechol-O-methyltransferase Homo sapiens 170-174 12083995-1 2002 Entacapone is one of a new class of drugs, the catechol-O-methyltransferase (COMT) inhibitors, which expand the therapeutic options for Parkinson"s disease by extending the action of levodopa. Levodopa 183-191 catechol-O-methyltransferase Homo sapiens 47-75 12083995-1 2002 Entacapone is one of a new class of drugs, the catechol-O-methyltransferase (COMT) inhibitors, which expand the therapeutic options for Parkinson"s disease by extending the action of levodopa. Levodopa 183-191 catechol-O-methyltransferase Homo sapiens 77-81 12075857-1 2002 One main metabolizing pathway of levodopa is O-methylation to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). Levodopa 33-41 catechol-O-methyltransferase Homo sapiens 88-116 11873938-4 2002 When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. Levodopa 154-162 catechol-O-methyltransferase Homo sapiens 61-65 11873938-6 2002 Differences in COMT activity may determine the individual response to levodopa and result in ethnic differences in PD susceptibility. Levodopa 70-78 catechol-O-methyltransferase Homo sapiens 15-19 12075857-1 2002 One main metabolizing pathway of levodopa is O-methylation to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). Levodopa 33-41 catechol-O-methyltransferase Homo sapiens 118-122 29712241-2 2001 Inhibition of COMT is of significant interest in the therapy of Parkinsonapos;s disease since it ensures that a larger percentage of orally administered L-dopa reaches-in the form of dopamine-its target in the brain. Levodopa 153-159 catechol-O-methyltransferase Homo sapiens 14-18 11978145-2 2002 Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Levodopa 54-62 catechol-O-methyltransferase Homo sapiens 256-284 11978145-2 2002 Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Levodopa 54-62 catechol-O-methyltransferase Homo sapiens 286-290 11978145-16 2002 The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 4-8 11978145-16 2002 The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. Levodopa 197-205 catechol-O-methyltransferase Homo sapiens 4-8 12390050-4 2002 Restoring traditional mealtimes and scheduling activities during predicted periods of sleepiness may help alleviate daytime somnolence; the use of controlled-release levodopa preparations or administration of a catechol-O-methyl transferase (COMT) inhibitor with levodopa at bedtime may reduce periods of night-time wakefulness. Levodopa 263-271 catechol-O-methyltransferase Homo sapiens 211-240 12390050-4 2002 Restoring traditional mealtimes and scheduling activities during predicted periods of sleepiness may help alleviate daytime somnolence; the use of controlled-release levodopa preparations or administration of a catechol-O-methyl transferase (COMT) inhibitor with levodopa at bedtime may reduce periods of night-time wakefulness. Levodopa 263-271 catechol-O-methyltransferase Homo sapiens 242-246 11793163-2 2002 The aim of the present investigation was to analyse the consequences of subsequent alterations in levodopa metabolism under common treatment conditions when the levodopa dose is adjusted due to the occurrence of dyskinesias after initiation of the COMT-inhibitor. Levodopa 98-106 catechol-O-methyltransferase Homo sapiens 248-252 11735324-3 2001 In the rat brain model L-DOPA and 3,4-dihydroxybenzoic acid were O-methylated mainly via S-COMT, while dopamine and noradrenaline, at low concentrations, were O-methylated slightly more by MB-COMT. Levodopa 23-29 catechol-O-methyltransferase Homo sapiens 91-95 11447722-5 2001 Beside levodopa a variety of alternative treatment options exists which enable a good and longer lasting control of symptoms (e.g. dopamine agonists, COMT-inhibitors etc.). Levodopa 7-15 catechol-O-methyltransferase Homo sapiens 150-154 11520127-0 2001 L-dopa upregulates the expression and activities of methionine adenosyl transferase and catechol-O-methyltransferase. Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 88-116 11520127-4 2001 In this study we investigated whether L-dopa increases the transmethylation process by inducing methionine adenosyl transferase (MAT), the enzyme that produces SAM, and catechol-O-methyl transferase (COMT), the enzyme that transfers the methyl group from SAM to L-dopa and DA. Levodopa 38-44 catechol-O-methyltransferase Homo sapiens 169-198 11520127-4 2001 In this study we investigated whether L-dopa increases the transmethylation process by inducing methionine adenosyl transferase (MAT), the enzyme that produces SAM, and catechol-O-methyl transferase (COMT), the enzyme that transfers the methyl group from SAM to L-dopa and DA. Levodopa 38-44 catechol-O-methyltransferase Homo sapiens 200-204 11520127-16 2001 The highlight of the study is the fact that L-dopa induces the enzymes MAT and COMT. Levodopa 44-50 catechol-O-methyltransferase Homo sapiens 79-83 11520127-18 2001 Thus, during PD treatment with L-dopa the induction of MAT and COMT is likely to occur and in turn increase the methylation and reduction of L-dopa and DA that may help cause the tolerance or the wearing-off effect developed to L-dopa. Levodopa 31-37 catechol-O-methyltransferase Homo sapiens 63-67 11693181-1 2001 Catechol-O-methyltransferase (COMT) inactivates neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Levodopa 103-111 catechol-O-methyltransferase Homo sapiens 0-28 11693181-1 2001 Catechol-O-methyltransferase (COMT) inactivates neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Levodopa 103-111 catechol-O-methyltransferase Homo sapiens 30-34 11498717-3 2001 Repeated high dose L-dopa administration was shown to induce marked dyskinesias in monkeys with an intact nigrostriatal system, and the threshold for dyskinesia expression was increased by peripheral catechol-O-methyltransferase inhibition with entacapone. Levodopa 19-25 catechol-O-methyltransferase Homo sapiens 200-228 11445284-2 2001 This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). Levodopa 29-37 catechol-O-methyltransferase Homo sapiens 67-95 11445284-2 2001 This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by catechol-O-methyltransferase (COMT). Levodopa 29-37 catechol-O-methyltransferase Homo sapiens 97-101 11440283-3 2001 Inhibition of COMT activity prolongs the action of levodopa and reduces fluctuations in response. Levodopa 51-59 catechol-O-methyltransferase Homo sapiens 14-18 11391126-12 2001 The study showed that repeated dosing of entacapone inhibits the COMT activity in a dose-dependent manner and thereby reduces the loss of L-Dopa to 3-OMD. Levodopa 138-144 catechol-O-methyltransferase Homo sapiens 65-69 11248589-1 2001 Tolcapone is a catechol-ortho-methyl-tranferase (COMT) inhibitor that increases the L-DOPA half-life and the duration of effect in Parkinson"s disease. Levodopa 84-90 catechol-O-methyltransferase Homo sapiens 15-47 11248589-1 2001 Tolcapone is a catechol-ortho-methyl-tranferase (COMT) inhibitor that increases the L-DOPA half-life and the duration of effect in Parkinson"s disease. Levodopa 84-90 catechol-O-methyltransferase Homo sapiens 49-53 11170218-1 2001 The aim was to investigate whether the improved 6-[(18)F]fluoro-L-dopa (FDOPA) availability induced by catechol-O-methyltransferase (COMT) inhibition can be more clearly seen during late than during standard (early) imaging in FDOPA uptake in Parkinson"s disease (PD) patients with severe dopaminergic hypofunction. Levodopa 63-70 catechol-O-methyltransferase Homo sapiens 103-131 11170218-1 2001 The aim was to investigate whether the improved 6-[(18)F]fluoro-L-dopa (FDOPA) availability induced by catechol-O-methyltransferase (COMT) inhibition can be more clearly seen during late than during standard (early) imaging in FDOPA uptake in Parkinson"s disease (PD) patients with severe dopaminergic hypofunction. Levodopa 63-70 catechol-O-methyltransferase Homo sapiens 133-137 11223018-8 2001 We conclude that supplementation with methionine, dimethionine or SAM ameliorates L-dopa neurotoxicity to dopamine neurons, while inhibition of COMT may aggravate or unmask L-dopa neurotoxicity. Levodopa 173-179 catechol-O-methyltransferase Homo sapiens 144-148 11223018-0 2001 COMT-dependent protection of dopaminergic neurons by methionine, dimethionine and S-adenosylmethionine (SAM) against L-dopa toxicity in vitro. Levodopa 117-123 catechol-O-methyltransferase Homo sapiens 0-4 11223018-3 2001 We hypothesized that SAM or SAM-precursors ameliorate L-dopa neurotoxicity, in a COMT-dependent fashion. Levodopa 54-60 catechol-O-methyltransferase Homo sapiens 81-85 11223018-7 2001 The COMT inhibitor dinitrocatechol (DNC) completely abolished the protective effect against L-dopa toxicity. Levodopa 92-98 catechol-O-methyltransferase Homo sapiens 4-8 11290882-1 2001 We have compared the effects of entacapone, a peripherally acting catechol-O-methyltransferase (COMT) inhibitor, and placebo on cardiovascular autonomic responses in L-Dopa/dopa decarboxylase inhibitor-treated patients with Parkinson"s disease (PD). Levodopa 166-172 catechol-O-methyltransferase Homo sapiens 96-100 11432539-1 2001 OBJECTIVE: To investigate the effect of administration of the catechol-Omethyltransferase (COMT) inhibitor tolcapone on the concentration-effect relationship of levodopa in patients with advanced Parkinson"s disease and on-off fluctuations. Levodopa 161-169 catechol-O-methyltransferase Homo sapiens 62-89 11432539-1 2001 OBJECTIVE: To investigate the effect of administration of the catechol-Omethyltransferase (COMT) inhibitor tolcapone on the concentration-effect relationship of levodopa in patients with advanced Parkinson"s disease and on-off fluctuations. Levodopa 161-169 catechol-O-methyltransferase Homo sapiens 91-95 11163295-7 2001 Thus, pharmacokinetic or pharmacodynamic factors other than the investigated genetic variant of the COMT enzyme seem to determine the response to levodopa in PD. Levodopa 146-154 catechol-O-methyltransferase Homo sapiens 100-104 11160877-8 2001 Among the catechol drugs used in the L-DOPA treatment of Parkinson"s disease, the COMT inhibitors entacapone and tolcapone were not methylated, whereas the DOPA decarboxylase inhibitor benserazide was 15 times more specific substrate than L-DOPA, the target of COMT inhibition. Levodopa 37-43 catechol-O-methyltransferase Homo sapiens 82-86 11290879-0 2001 Catechol-O-methyltransferase decreases levodopa toxicity in vitro. Levodopa 39-47 catechol-O-methyltransferase Homo sapiens 0-28 11290879-1 2001 The purpose of this study was to examine the effects of 3-O-methylation by catechol-O-methyltransferase (COMT) on the toxicity of levodopa in neuronal cultures. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 75-103 11290879-1 2001 The purpose of this study was to examine the effects of 3-O-methylation by catechol-O-methyltransferase (COMT) on the toxicity of levodopa in neuronal cultures. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 105-109 11290879-5 2001 A possible defense mechanism is by means of metabolic shunting of levodopa excess to 3-O-methyldopa by COMT in peripheral and central nervous system tissues. Levodopa 66-74 catechol-O-methyltransferase Homo sapiens 103-107 11290879-6 2001 In this study we examine whether the use of COMT inhibitor, which reduced the levels of 3-O-methyldopa, affect levodopa toxicity. Levodopa 111-119 catechol-O-methyltransferase Homo sapiens 44-48 11290879-10 2001 Addition of purified COMT to levodopa prevented its auto-oxidation and markedly attenuated its cytotoxicity in vitro. Levodopa 29-37 catechol-O-methyltransferase Homo sapiens 21-25 11290879-13 2001 Catechol-O-methyltransferase attenuates toxicity of levodopa in vitro by its metabolism to nontoxic 3-O-methyldopa. Levodopa 52-60 catechol-O-methyltransferase Homo sapiens 0-28 11346021-5 2001 A more recent strategy has centered on increasing the availability of intracellular levodopa and synaptic dopamine by inhibiting the peripheral and central metabolism of levodopa to 3-O-methyldopa with the use of a catechol-O-methyltransferase inhibitor. Levodopa 84-92 catechol-O-methyltransferase Homo sapiens 215-243 11346021-5 2001 A more recent strategy has centered on increasing the availability of intracellular levodopa and synaptic dopamine by inhibiting the peripheral and central metabolism of levodopa to 3-O-methyldopa with the use of a catechol-O-methyltransferase inhibitor. Levodopa 170-178 catechol-O-methyltransferase Homo sapiens 215-243 11244687-10 2000 Levodopa was prescript to 70.9%, anticholinergic to 51.3%, MAO-B-I to 33.4%, amantadine to 33.1%, D2 stimulants to 18.5%, and COMT-I to 2.6%. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 126-130 10900396-1 2000 Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Levodopa 127-133 catechol-O-methyltransferase Homo sapiens 9-37 11058906-1 2000 Catechol-O-methyltransferase (COMT) catalyses the O-methylation of neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Levodopa 122-130 catechol-O-methyltransferase Homo sapiens 0-28 11058906-1 2000 Catechol-O-methyltransferase (COMT) catalyses the O-methylation of neurotransmitters, catechol hormones and drugs such as levodopa and methyldopa. Levodopa 122-130 catechol-O-methyltransferase Homo sapiens 30-34 11029227-8 2000 Dopamine agonists, catechol-o-methyltransferase inhibitors, amantadine and apomorphine have differing but beneficial roles in the management of levodopa side effects. Levodopa 144-152 catechol-O-methyltransferase Homo sapiens 19-47 10900396-1 2000 Both the catechol-O-methyltransferase (COMT) inhibitor entacapone and the monoamine oxidase B (MAO-B) inhibitor selegiline are L-dopa extenders. Levodopa 127-133 catechol-O-methyltransferase Homo sapiens 39-43 10900397-1 2000 Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson"s disease (PD) patients in chronic Levodopa (L-dopa) therapy. Levodopa 205-213 catechol-O-methyltransferase Homo sapiens 92-96 10900397-1 2000 Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson"s disease (PD) patients in chronic Levodopa (L-dopa) therapy. Levodopa 215-221 catechol-O-methyltransferase Homo sapiens 62-90 10900397-1 2000 Following the introduction of tolcapone, a potent, reversible Catechol-O-methyltransferase (COMT) inhibitor, it has been possible to optimise the management of Parkinson"s disease (PD) patients in chronic Levodopa (L-dopa) therapy. Levodopa 215-221 catechol-O-methyltransferase Homo sapiens 92-96 11052229-4 2000 Administering L-dopa with a catechol-O-methyltransferase (COMT) inhibitor to block its peripheral metabolism increases its plasma half-life and might have a similar effect. Levodopa 14-20 catechol-O-methyltransferase Homo sapiens 28-56 11052229-4 2000 Administering L-dopa with a catechol-O-methyltransferase (COMT) inhibitor to block its peripheral metabolism increases its plasma half-life and might have a similar effect. Levodopa 14-20 catechol-O-methyltransferase Homo sapiens 58-62 11147506-4 2000 Levodopa is metabolized by both decarboxylase and catechol-O-methyl transferase enzymes. Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 50-79 10981253-6 2000 DATA SYNTHESIS: Entacapone is the second medication of a new class of drugs, the catechol-O-methyltransferase inhibitors, indicated for clinical use as an adjunct to levodopa/carbidopa to treat patients with idiopathic Parkinson"s disease who experience the signs and symptoms of end-of-dose wearing-off. Levodopa 166-174 catechol-O-methyltransferase Homo sapiens 81-109 10898900-2 2000 The enzyme catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamines such as dopamine, L-DOPA, adrenaline, and noradrenaline and therefore could be considered as a candidate locus for ADHD susceptibility. Levodopa 119-125 catechol-O-methyltransferase Homo sapiens 11-39 10898900-2 2000 The enzyme catechol-O-methyltransferase (COMT) plays a key role in the degradation of catecholamines such as dopamine, L-DOPA, adrenaline, and noradrenaline and therefore could be considered as a candidate locus for ADHD susceptibility. Levodopa 119-125 catechol-O-methyltransferase Homo sapiens 41-45 10882160-1 2000 When peripheral decarboxylation is blocked by carbidopa or benserazide, the main metabolic pathway of levodopa is O-methylation by catechol-O-methyltransferase (COMT). Levodopa 102-110 catechol-O-methyltransferase Homo sapiens 131-159 10882160-1 2000 When peripheral decarboxylation is blocked by carbidopa or benserazide, the main metabolic pathway of levodopa is O-methylation by catechol-O-methyltransferase (COMT). Levodopa 102-110 catechol-O-methyltransferase Homo sapiens 161-165 10882160-24 2000 COMT inhibitors added to levodopa therapy are beneficial, particularly in patients with fluctuating disease. Levodopa 25-33 catechol-O-methyltransferase Homo sapiens 0-4 10834300-3 2000 Chronic L-dopa induces catechol-O-methyltransferase (COMT) and methionine adenosyl transferase (MAT), enzymes involved in the methylation of catecholamines (CA). Levodopa 8-14 catechol-O-methyltransferase Homo sapiens 23-51 10834300-3 2000 Chronic L-dopa induces catechol-O-methyltransferase (COMT) and methionine adenosyl transferase (MAT), enzymes involved in the methylation of catecholamines (CA). Levodopa 8-14 catechol-O-methyltransferase Homo sapiens 53-57 10692500-0 2000 Catechol-O-methyltransferase inhibition attenuates levodopa toxicity in mesencephalic dopamine neurons. Levodopa 51-59 catechol-O-methyltransferase Homo sapiens 0-28 10692500-8 2000 Furthermore, the primary metabolite of L-dopa formed by COMT, 3-O-methyldopa, and the methyl group donor S-adenosyl-L-methionine used by COMT did not alter THir neuron survival and L-dopa-induced toxicity, respectively, with concentrations up to 100 microM. Levodopa 39-45 catechol-O-methyltransferase Homo sapiens 56-60 10692500-9 2000 These data demonstrate that COMT inhibition attenuates L-dopa toxicity toward DA neurons in vitro, but probably not by preventing 3-O-methyldopa production or cellular S-adenosyl-L-methionine depletion. Levodopa 55-61 catechol-O-methyltransferase Homo sapiens 28-32 11147511-1 2000 Two inhibitors of catechol-O-methyl transferase (COMT), tolcapone and entacapone, have recently been introduced as adjuncts to levodopa in the treatment of Parkinson"s disease patients. Levodopa 127-135 catechol-O-methyltransferase Homo sapiens 49-53 11147512-1 2000 Catechol-O-methyl transferase (COMT) inhibitors block the peripheral metabolism of levodopa, increase its plasma half-life, and enhance its brain availability. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 0-29 11147512-1 2000 Catechol-O-methyl transferase (COMT) inhibitors block the peripheral metabolism of levodopa, increase its plasma half-life, and enhance its brain availability. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 31-35 11147512-2 2000 Two COMT inhibitors, tolcapone and entacapone, have recently been made available as adjunctive agents to levodopa. Levodopa 105-113 catechol-O-methyltransferase Homo sapiens 4-8 11147512-7 2000 Finally, there are theoretical reasons to consider administering a COMT inhibitor to patients from the onset of levodopa therapy in order to reduce the likelihood that motor complications will develop. Levodopa 112-120 catechol-O-methyltransferase Homo sapiens 67-71 11147513-4 2000 Administration of levodopa with a catechol-O-methyl transferase (COMT) inhibitor increases its plasma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. Levodopa 18-26 catechol-O-methyltransferase Homo sapiens 34-63 11147513-4 2000 Administration of levodopa with a catechol-O-methyl transferase (COMT) inhibitor increases its plasma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. Levodopa 18-26 catechol-O-methyltransferase Homo sapiens 65-69 11147513-4 2000 Administration of levodopa with a catechol-O-methyl transferase (COMT) inhibitor increases its plasma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. Levodopa 158-166 catechol-O-methyltransferase Homo sapiens 34-63 11147513-4 2000 Administration of levodopa with a catechol-O-methyl transferase (COMT) inhibitor increases its plasma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. Levodopa 158-166 catechol-O-methyltransferase Homo sapiens 65-69 11147513-5 2000 We hypothesize that the risk of developing motor complications in PD patients when levodopa is introduced can be reduced if the levodopa is coupled with a COMT inhibitor so as to provide more continuous dopaminergic stimulation of dopamine receptors. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 155-159 10637595-0 2000 US licence for COMT inhibitor to boost levodopa effect in Parkinson"s. Levodopa 39-47 catechol-O-methyltransferase Homo sapiens 15-19 10641989-3 2000 In addition, a new class of drugs, catechol-O-methyltransferase inhibitors, can extend the duration of levodopa action. Levodopa 103-111 catechol-O-methyltransferase Homo sapiens 35-63 10641990-7 2000 Addition of a catechol-O-methyltransferase inhibitor can increase the duration of levodopa"s effect and may prove especially valuable for patients who experience early wearing off of levodopa. Levodopa 82-90 catechol-O-methyltransferase Homo sapiens 14-42 10641990-7 2000 Addition of a catechol-O-methyltransferase inhibitor can increase the duration of levodopa"s effect and may prove especially valuable for patients who experience early wearing off of levodopa. Levodopa 183-191 catechol-O-methyltransferase Homo sapiens 14-42 10855610-2 2000 COMT inhibitors act by extending the duration of action of levodopa, thus improving the amount of time a patient can experience benefit from levodopa. Levodopa 59-67 catechol-O-methyltransferase Homo sapiens 0-4 10855610-2 2000 COMT inhibitors act by extending the duration of action of levodopa, thus improving the amount of time a patient can experience benefit from levodopa. Levodopa 141-149 catechol-O-methyltransferase Homo sapiens 0-4 10855610-3 2000 COMT inhibitors are only used in conjunction with levodopa. Levodopa 50-58 catechol-O-methyltransferase Homo sapiens 0-4 10855610-7 2000 This article also provides representative case histories for the appropriate use of COMT inhibitors that illustrate how these drugs can be used to manage patients with a fluctuating response to levodopa. Levodopa 194-202 catechol-O-methyltransferase Homo sapiens 84-88 10834300-11 2000 L-dopa produces high levels of DA and induces MAT and COMT. Levodopa 0-6 catechol-O-methyltransferase Homo sapiens 54-58 11147506-6 2000 More recent studies suggest that combination of levodopa with an inhibitor of catechol-O-methyl transferase prolongs the duration of effect of the drug and can prolong the duration of motor response in fluctuating patients. Levodopa 48-56 catechol-O-methyltransferase Homo sapiens 78-107 10555944-7 1999 The catechol-O-methyltransferase inhibitors that block a compensatory metabolic pathway for levodopa and prolong its duration may improve the consistency of the dopaminergic response. Levodopa 92-100 catechol-O-methyltransferase Homo sapiens 4-32 10555945-3 1999 The need to extend the actions of levodopa led to the development of the catechol-O-methyltransferase (COMT) inhibitors, which are the newest agents introduced to manage the symptoms of Parkinson"s disease. Levodopa 34-42 catechol-O-methyltransferase Homo sapiens 73-101 10555945-3 1999 The need to extend the actions of levodopa led to the development of the catechol-O-methyltransferase (COMT) inhibitors, which are the newest agents introduced to manage the symptoms of Parkinson"s disease. Levodopa 34-42 catechol-O-methyltransferase Homo sapiens 103-107 10555945-4 1999 Entacapone and tolcapone are two potent, selective, and reversible COMT inhibitors that effectively augment levodopa"s pharmacokinetics by increasing area under the plasma concentration versus time curve and plasma elimination half-life without significantly affecting peak levodopa concentrations. Levodopa 108-116 catechol-O-methyltransferase Homo sapiens 67-71 10555945-4 1999 Entacapone and tolcapone are two potent, selective, and reversible COMT inhibitors that effectively augment levodopa"s pharmacokinetics by increasing area under the plasma concentration versus time curve and plasma elimination half-life without significantly affecting peak levodopa concentrations. Levodopa 274-282 catechol-O-methyltransferase Homo sapiens 67-71 10555945-8 1999 These data, combined with the potential for delaying the onset of motor fluctuations, suggest that COMT inhibition may enhance levodopa"s short- and long-term efficacy. Levodopa 127-135 catechol-O-methyltransferase Homo sapiens 99-103 11139811-5 1999 Dopamine agonists and catechol-O-methyl-transferase (COMT) inhibitors have been valuable adjuncts to levodopa, but until now levodopa has remained the cornerstone of therapy. Levodopa 101-109 catechol-O-methyltransferase Homo sapiens 22-51 11139811-5 1999 Dopamine agonists and catechol-O-methyl-transferase (COMT) inhibitors have been valuable adjuncts to levodopa, but until now levodopa has remained the cornerstone of therapy. Levodopa 101-109 catechol-O-methyltransferase Homo sapiens 53-57 11147507-2 2000 However, exogenously administered levodopa is extensively metabolized in the periphery by aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) so that only 1% of an administered dose gains access to the brain. Levodopa 34-42 catechol-O-methyltransferase Homo sapiens 135-163 11147507-2 2000 However, exogenously administered levodopa is extensively metabolized in the periphery by aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) so that only 1% of an administered dose gains access to the brain. Levodopa 34-42 catechol-O-methyltransferase Homo sapiens 165-169 11147507-3 2000 Even when levodopa is co-administered with an inhibitor of AAAD such as benserazide or carbidopa, the bulk (90%) of levodopa is converted by COMT to the therapeutically inactive 3-O-methyldopa. Levodopa 10-18 catechol-O-methyltransferase Homo sapiens 141-145 11147507-3 2000 Even when levodopa is co-administered with an inhibitor of AAAD such as benserazide or carbidopa, the bulk (90%) of levodopa is converted by COMT to the therapeutically inactive 3-O-methyldopa. Levodopa 116-124 catechol-O-methyltransferase Homo sapiens 141-145 11147507-4 2000 Two COMT inhibitors, tolcapone and entacapone, have recently been introduced as adjuncts to levodopa to further inhibit peripheral levodopa metabolism and thereby enhance brain levodopa availability. Levodopa 131-139 catechol-O-methyltransferase Homo sapiens 4-8 11147507-4 2000 Two COMT inhibitors, tolcapone and entacapone, have recently been introduced as adjuncts to levodopa to further inhibit peripheral levodopa metabolism and thereby enhance brain levodopa availability. Levodopa 131-139 catechol-O-methyltransferase Homo sapiens 4-8 11147508-0 2000 Effect of COMT inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Levodopa 74-82 catechol-O-methyltransferase Homo sapiens 10-14 11147508-1 2000 Catechol-O-methyl transferase (COMT) is one of the principal levodopa-metabolizing enzymes, particularly when aromatic amino acid decarboxylase (AAAD) is partially inhibited by carbidopa or benserazide. Levodopa 61-69 catechol-O-methyltransferase Homo sapiens 0-29 11147508-1 2000 Catechol-O-methyl transferase (COMT) is one of the principal levodopa-metabolizing enzymes, particularly when aromatic amino acid decarboxylase (AAAD) is partially inhibited by carbidopa or benserazide. Levodopa 61-69 catechol-O-methyltransferase Homo sapiens 31-35 11147509-0 2000 Benefits of COMT inhibitors in levodopa-treated parkinsonian patients: results of clinical trials. Levodopa 31-39 catechol-O-methyltransferase Homo sapiens 12-16 10510160-1 1999 AIMS: Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson"s disease. Levodopa 95-103 catechol-O-methyltransferase Homo sapiens 27-55 10510160-1 1999 AIMS: Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson"s disease. Levodopa 95-103 catechol-O-methyltransferase Homo sapiens 57-61 12973467-1 1999 Catechol O-methyltransferase (COMT) inhibition has been proposed as a means to increase levodopa bioavailability in patients with Parkinson"s disease, which may be useful in reducing the total dose of levodopa, diminishing its frequency of administration and, more importantly, improving fluctuations in the response to each individual dose of levodopa, which usually develop after chronic treatment. Levodopa 88-96 catechol-O-methyltransferase Homo sapiens 0-28 12973467-1 1999 Catechol O-methyltransferase (COMT) inhibition has been proposed as a means to increase levodopa bioavailability in patients with Parkinson"s disease, which may be useful in reducing the total dose of levodopa, diminishing its frequency of administration and, more importantly, improving fluctuations in the response to each individual dose of levodopa, which usually develop after chronic treatment. Levodopa 88-96 catechol-O-methyltransferase Homo sapiens 30-34 12973467-1 1999 Catechol O-methyltransferase (COMT) inhibition has been proposed as a means to increase levodopa bioavailability in patients with Parkinson"s disease, which may be useful in reducing the total dose of levodopa, diminishing its frequency of administration and, more importantly, improving fluctuations in the response to each individual dose of levodopa, which usually develop after chronic treatment. Levodopa 201-209 catechol-O-methyltransferase Homo sapiens 0-28 12973467-1 1999 Catechol O-methyltransferase (COMT) inhibition has been proposed as a means to increase levodopa bioavailability in patients with Parkinson"s disease, which may be useful in reducing the total dose of levodopa, diminishing its frequency of administration and, more importantly, improving fluctuations in the response to each individual dose of levodopa, which usually develop after chronic treatment. Levodopa 201-209 catechol-O-methyltransferase Homo sapiens 30-34 12973467-1 1999 Catechol O-methyltransferase (COMT) inhibition has been proposed as a means to increase levodopa bioavailability in patients with Parkinson"s disease, which may be useful in reducing the total dose of levodopa, diminishing its frequency of administration and, more importantly, improving fluctuations in the response to each individual dose of levodopa, which usually develop after chronic treatment. Levodopa 201-209 catechol-O-methyltransferase Homo sapiens 0-28 12973467-1 1999 Catechol O-methyltransferase (COMT) inhibition has been proposed as a means to increase levodopa bioavailability in patients with Parkinson"s disease, which may be useful in reducing the total dose of levodopa, diminishing its frequency of administration and, more importantly, improving fluctuations in the response to each individual dose of levodopa, which usually develop after chronic treatment. Levodopa 201-209 catechol-O-methyltransferase Homo sapiens 30-34 12973467-2 1999 Entacapone is a potent, selective peripheral catechol O-methyltransferase inhibitor which effectively inhibits the O-methylation of levodopa, thus increasing its central bioavailability and potentiating its behavioral effects. Levodopa 132-140 catechol-O-methyltransferase Homo sapiens 45-73 9633684-0 1998 Extending levodopa action: COMT inhibition. Levodopa 10-18 catechol-O-methyltransferase Homo sapiens 27-31 10229966-0 1999 [Entacapone++ : a new catechol-O-methyltransferase inhibitor which improves the response to levodopa in patients with Parkinson disease and fluctuating motor function]. Levodopa 92-100 catechol-O-methyltransferase Homo sapiens 22-50 10047930-1 1999 Tolcapone, a central and peripheral catechol O-methyltransferase (COMT) inhibitor, reduces the conversion of L-Dopa into 3-O-methyl-Dopa (3-OMD), thus leading to more stable and sustained L-Dopa plasma levels. Levodopa 109-115 catechol-O-methyltransferase Homo sapiens 36-64 10047930-1 1999 Tolcapone, a central and peripheral catechol O-methyltransferase (COMT) inhibitor, reduces the conversion of L-Dopa into 3-O-methyl-Dopa (3-OMD), thus leading to more stable and sustained L-Dopa plasma levels. Levodopa 109-115 catechol-O-methyltransferase Homo sapiens 66-70 10047930-1 1999 Tolcapone, a central and peripheral catechol O-methyltransferase (COMT) inhibitor, reduces the conversion of L-Dopa into 3-O-methyl-Dopa (3-OMD), thus leading to more stable and sustained L-Dopa plasma levels. Levodopa 188-194 catechol-O-methyltransferase Homo sapiens 66-70 10343151-0 1999 COMT inhibition by tolcapone further improves levodopa pharmacokinetics when combined with a dual-release formulation of levodopa/benserazide. Levodopa 46-54 catechol-O-methyltransferase Homo sapiens 0-4 10343151-2 1999 The objective of the study reported here was the investigation of the effect of catechol-O-methyl transferase (COMT) inhibition by tolcapone on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new dual-release formulation (dual-RF) of levodopa/benserazide (200/50). Levodopa 168-176 catechol-O-methyltransferase Homo sapiens 80-109 10343151-2 1999 The objective of the study reported here was the investigation of the effect of catechol-O-methyl transferase (COMT) inhibition by tolcapone on the pharmacokinetics of levodopa and 3-O-methyldopa (3-OMD) after administration of a new dual-release formulation (dual-RF) of levodopa/benserazide (200/50). Levodopa 168-176 catechol-O-methyltransferase Homo sapiens 111-115 10370911-12 1999 Addition of dopamine agonists, MAO-B inhibitors, COMT inhibitors and controlled release levodopa preparations may be helpful in prolonging the duration of efficacy of each single levodopa dose. Levodopa 179-187 catechol-O-methyltransferase Homo sapiens 49-53 10051176-2 1999 However, its benefits are limited owing to extensive metabolism by catechol-O-methyltransferase (COMT), especially if levodopa is used in combination with peripheral dopa-decarboxylase inhibitors. Levodopa 118-126 catechol-O-methyltransferase Homo sapiens 67-95 10051176-2 1999 However, its benefits are limited owing to extensive metabolism by catechol-O-methyltransferase (COMT), especially if levodopa is used in combination with peripheral dopa-decarboxylase inhibitors. Levodopa 118-126 catechol-O-methyltransferase Homo sapiens 97-101 10051176-5 1999 Preclinical and clinical studies have shown that COMT inhibitors markedly enhance levodopa availability and prolong its plasma half-life. Levodopa 82-90 catechol-O-methyltransferase Homo sapiens 49-53 10051176-8 1999 COMT inhibition promises to become an important means of extending the benefits of levodopa therapy in PD. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 0-4 10451758-2 1999 By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier. Levodopa 102-110 catechol-O-methyltransferase Homo sapiens 25-54 10451758-2 1999 By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier. Levodopa 102-110 catechol-O-methyltransferase Homo sapiens 56-60 10451758-4 1999 Clinical studies with COMT inhibitors have shown benefit in both stable and fluctuating PD patients with improvement in motor function with lower levodopa doses. Levodopa 146-154 catechol-O-methyltransferase Homo sapiens 22-26 10407949-3 1999 COMT inhibitors enhance and prolong the effect of single levodopa doses. Levodopa 57-65 catechol-O-methyltransferase Homo sapiens 0-4 15992091-3 1999 Entacapone (Comtan) is a selective, reversible catechol-O-methyltransferase inhibitor that dose-dependently increases the peripheral bioavailability of levodopa and prolongs its duration of action. Levodopa 152-160 catechol-O-methyltransferase Homo sapiens 47-75 9917075-1 1999 Tolcapone is a selective peripheral and central catechol-O-methyltransferase (COMT) inhibitor recently approved as adjunctive therapy in patients with idiopathic Parkinson"s disease who are already being treated with a levodopa-peripheral dopa decarboxylase inhibitor (DDI) combination. Levodopa 219-227 catechol-O-methyltransferase Homo sapiens 78-82 9818851-3 1998 BACKGROUND: Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that has been shown to increase the area under the concentration-time curve of plasma levodopa by decreasing its systemic elimination, thereby promoting and improving therapeutic response to it. Levodopa 160-168 catechol-O-methyltransferase Homo sapiens 28-56 9818851-3 1998 BACKGROUND: Entacapone is a catechol-O-methyltransferase (COMT) inhibitor that has been shown to increase the area under the concentration-time curve of plasma levodopa by decreasing its systemic elimination, thereby promoting and improving therapeutic response to it. Levodopa 160-168 catechol-O-methyltransferase Homo sapiens 58-62 9708959-2 1998 OBJECTIVE: To assess the efficacy and tolerability of the catechol-O-methyltransferase inhibitor tolcapone in reducing "off/on" fluctuations in levodopa-treated parkinsonian patients. Levodopa 144-152 catechol-O-methyltransferase Homo sapiens 58-86 9633680-3 1998 Levodopa is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT). Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 117-145 9633680-3 1998 Levodopa is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT). Levodopa 0-8 catechol-O-methyltransferase Homo sapiens 147-151 9633680-4 1998 Because gastric AADC and COMT degrade levodopa, the drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors of COMT will also enter clinical use. Levodopa 38-46 catechol-O-methyltransferase Homo sapiens 25-29 9682265-1 1998 Catechol O-methyltransferase (COMT) inactivates neurotransmitters, hormones and drugs such as levodopa. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 0-28 9682265-1 1998 Catechol O-methyltransferase (COMT) inactivates neurotransmitters, hormones and drugs such as levodopa. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 30-34 9633684-3 1998 Therefore, inhibiting COMT activity is one method of extending the action of levodopa. Levodopa 77-85 catechol-O-methyltransferase Homo sapiens 22-26 9633684-5 1998 COMT inhibitors increase patients" duration of response to levodopa and reduce response fluctuations. Levodopa 59-67 catechol-O-methyltransferase Homo sapiens 0-4 9591516-4 1998 This review focuses on the role of the new catechol O-methyltransferase (COMT) inhibitors tolcapone and entacapone as adjuncts to levodopa therapy. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 43-71 9591516-4 1998 This review focuses on the role of the new catechol O-methyltransferase (COMT) inhibitors tolcapone and entacapone as adjuncts to levodopa therapy. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 73-77 9591519-0 1998 Influence of COMT inhibition on levodopa pharmacology and therapy. Levodopa 32-40 catechol-O-methyltransferase Homo sapiens 13-17 9591519-1 1998 Catechol O-methyltransferase (COMT) is an important enzyme that is linked directly to therapy with levodopa. Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 0-28 9591519-1 1998 Catechol O-methyltransferase (COMT) is an important enzyme that is linked directly to therapy with levodopa. Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 30-34 9591519-4 1998 With COMT inhibition, greater peripheral bioavailability of levodopa occurs in humans without an enhancement of peak plasma levels. Levodopa 60-68 catechol-O-methyltransferase Homo sapiens 5-9 9591519-5 1998 It is reasonable to suggest that COMT inhibition will be associated with prolonged effects of levodopa in PD, without increased peak dose toxicity in the form of dyskinesias and hallucinations. Levodopa 94-102 catechol-O-methyltransferase Homo sapiens 33-37 9591520-1 1998 Tolcapone is a potent, reversible inhibitor of catechol O-methyltransferase (COMT) intended for use as an adjunct to levodopa therapy for Parkinson"s disease (PD). Levodopa 117-125 catechol-O-methyltransferase Homo sapiens 47-75 9591522-0 1998 Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients. Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 0-28 9591522-2 1998 Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 14-42 9591522-2 1998 Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. Levodopa 177-185 catechol-O-methyltransferase Homo sapiens 14-42 9426871-1 1997 New medications recently developed for treating Parkinson"s disease include two inhibitors of catechol-O-methyltransferase (COMT), entacapone and tolcapone, which, by decreasing the elimination of levodopa, extend the duration of its effects. Levodopa 197-205 catechol-O-methyltransferase Homo sapiens 94-122 9591224-1 1998 Clinical pharmacology studies have shown that the catechol-O-methyltransferase inhibitor tolcapone increases the bioavailability area under the plasma concentration-time curve (AUC) and the plasma elimination half-life (t1/2) of levodopa. Levodopa 229-237 catechol-O-methyltransferase Homo sapiens 50-78 9352569-1 1997 Catechol-O-methyltransferase catalyses the O-methylation of biologically active or toxic catechols and is a major component of the metabolism of drugs and neurotransmitters such as L-dopa, noradrenaline, adrenaline, and dopamine. Levodopa 181-187 catechol-O-methyltransferase Homo sapiens 0-28 9251066-0 1997 Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson"s disease. Levodopa 42-48 catechol-O-methyltransferase Homo sapiens 23-27 9403227-1 1997 Tolcapone (Ro 40-7592) is a novel inhibitor of catechol-O-methyltransferase that is being developed for clinical use in the treatment of Parkinson"s disease as add-on therapy to a combination of levodopa and a peripheral amino acid decarboxylase inhibitor (benserazide or carbidopa). Levodopa 195-203 catechol-O-methyltransferase Homo sapiens 47-75 9392574-3 1997 Entacapone, a peripherally acting, reversible inhibitor of catechol-O-methyltransferase, slows the elimination of levodopa in humans by reducing the formation of 3-O-methyldopa. Levodopa 114-122 catechol-O-methyltransferase Homo sapiens 59-87 9337447-13 1997 The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson"s disease. Levodopa 79-87 catechol-O-methyltransferase Homo sapiens 4-8 9337447-13 1997 The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson"s disease. Levodopa 288-296 catechol-O-methyltransferase Homo sapiens 4-8 9343116-0 1997 Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients. Levodopa 96-104 catechol-O-methyltransferase Homo sapiens 0-28 9343116-2 1997 Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. Levodopa 83-91 catechol-O-methyltransferase Homo sapiens 14-42 9343116-2 1997 Inhibition of catechol-O-methyltransferase by tolcapone has been shown to increase levodopa bioavailability and plasma elimination half life, thereby prolonging the efficacy of levodopa. Levodopa 177-185 catechol-O-methyltransferase Homo sapiens 14-42 9333106-8 1997 RESULTS: By inhibiting COMT, tolcapone reduced levodopa metabolism to 3-O-methyldopa, resulting in a twofold increase in levodopa exposure (area under the curve) and elimination half-life, without changing levodopa peak plasma concentration. Levodopa 47-55 catechol-O-methyltransferase Homo sapiens 23-27 9333106-8 1997 RESULTS: By inhibiting COMT, tolcapone reduced levodopa metabolism to 3-O-methyldopa, resulting in a twofold increase in levodopa exposure (area under the curve) and elimination half-life, without changing levodopa peak plasma concentration. Levodopa 121-129 catechol-O-methyltransferase Homo sapiens 23-27 9333106-8 1997 RESULTS: By inhibiting COMT, tolcapone reduced levodopa metabolism to 3-O-methyldopa, resulting in a twofold increase in levodopa exposure (area under the curve) and elimination half-life, without changing levodopa peak plasma concentration. Levodopa 121-129 catechol-O-methyltransferase Homo sapiens 23-27 9175615-7 1997 As compared to peripheral COMT inhibitors, this central effect may help preserve and stabilize the synaptic levels of DA and, thus, further improve the effects of L-DOPA therapy in parkinsonian patients. Levodopa 163-169 catechol-O-methyltransferase Homo sapiens 26-30 9121699-1 1997 Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines such as adrenaline, noradrenaline, dopamine, and levodopa. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 0-28 9121699-1 1997 Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines such as adrenaline, noradrenaline, dopamine, and levodopa. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 30-34 9008498-2 1997 Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the plasma half-life of levodopa. Levodopa 99-107 catechol-O-methyltransferase Homo sapiens 22-50 9252801-1 1997 This double-blind, placebo-controlled, randomized, crossover study was designed to evaluate the effects of catechol-O-methyltransferase (COMT) inhibition by tolcapone on the pharmacokinetics of levodopa given as four different formulations of levodopa/benserazide: 50/12.5 mg, 100/25 mg, 200/50 mg (all standard release), or 100/25 mg (controlled release). Levodopa 194-202 catechol-O-methyltransferase Homo sapiens 137-141 9014452-3 1997 FDOPA is also an efficient tracer to analyze pharmacokinetics of L-DOPA by measuring radioactivities of its metabolites in the peripheral blood by HPLC and to evaluate pharmacological effects on dopamine metabolism by pretreatment of dopa decarboxylase inhibitor or COMT inhibitor. Levodopa 65-71 catechol-O-methyltransferase Homo sapiens 266-270 9426871-1 1997 New medications recently developed for treating Parkinson"s disease include two inhibitors of catechol-O-methyltransferase (COMT), entacapone and tolcapone, which, by decreasing the elimination of levodopa, extend the duration of its effects. Levodopa 197-205 catechol-O-methyltransferase Homo sapiens 124-128 8941353-7 1996 However it remains possible that allelic variation in COMT influences severity, type of pathology or treatment response to levodopa or COMT inhibitors. Levodopa 123-131 catechol-O-methyltransferase Homo sapiens 54-58 8836986-4 1996 On the other hand, by administration of L-DOPA combined with L-threo-DOPS, the levels of monoamines increased in general, whereas the monoamine metabolites by catechol-O-methyltransferase were reduced compared with those in the patients treated with L-DOPA alone. Levodopa 40-46 catechol-O-methyltransferase Homo sapiens 159-187 8836986-4 1996 On the other hand, by administration of L-DOPA combined with L-threo-DOPS, the levels of monoamines increased in general, whereas the monoamine metabolites by catechol-O-methyltransferase were reduced compared with those in the patients treated with L-DOPA alone. Levodopa 250-256 catechol-O-methyltransferase Homo sapiens 159-187 8527287-0 1995 Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa. Levodopa 97-105 catechol-O-methyltransferase Homo sapiens 56-60 8726541-0 1996 Effect of one month"s treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients. Levodopa 151-159 catechol-O-methyltransferase Homo sapiens 57-85 8726541-8 1996 Peripheral COMT inhibition with entacapone increased significantly the bioavailability of levodopa and prolonged its antiparkinsonian effect after a single dose and after repeated dosing for 4 weeks. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 11-15 8807664-1 1996 Catechol-O-methyltransferase (COMT) inactivates catecholamines and catechol drugs such as L-DOPA. Levodopa 90-96 catechol-O-methyltransferase Homo sapiens 0-28 8807664-1 1996 Catechol-O-methyltransferase (COMT) inactivates catecholamines and catechol drugs such as L-DOPA. Levodopa 90-96 catechol-O-methyltransferase Homo sapiens 30-34 8787797-6 1995 The proposed pharmacokinetic model and the evaluation of carbidopa in this study will provide useful information for the development of drug delivery systems for levodopa or catechol-O-methyltransferase inhibitors, for further stabilization of plasma concentrations of levodopa in parkinsonian patients. Levodopa 269-277 catechol-O-methyltransferase Homo sapiens 174-202 8615170-0 1996 Effects of catechol-O-methyltransferase (COMT) inhibition on the pharmacokinetics of L-DOPA. Levodopa 85-91 catechol-O-methyltransferase Homo sapiens 11-39 8615170-0 1996 Effects of catechol-O-methyltransferase (COMT) inhibition on the pharmacokinetics of L-DOPA. Levodopa 85-91 catechol-O-methyltransferase Homo sapiens 41-45 8635184-1 1995 Tolcapone, a catechol-O-methyltransferase inhibitor, can interfere with the metabolism of levodopa and dopamine and could prolong the motor effect induced by levodopa in parkinsonian patients. Levodopa 90-98 catechol-O-methyltransferase Homo sapiens 13-41 7651456-7 1995 The acute inhibition of amino acid decarboxylase, monoamine oxidase-B, and COMT is well tolerated and prolongs the L-DOPA response in PD patients. Levodopa 115-121 catechol-O-methyltransferase Homo sapiens 75-79 8665534-1 1995 We studied the effect of entacapone, a catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of a controlled-release (CR) levodopa-carbidopa preparation (Sinemet CR) in an open, randomized trial in 12 healthy male volunteers. Levodopa 128-136 catechol-O-methyltransferase Homo sapiens 69-73 8665546-0 1995 Acute effects of COMT inhibition on L-DOPA pharmacokinetics in patients treated with carbidopa and selegiline. Levodopa 36-42 catechol-O-methyltransferase Homo sapiens 17-21 8665546-1 1995 The effects of acute catechol-O-methyltransferase (COMT) inhibition on L-DOPA pharmacokinetics were studied in 10 parkinsonian subjects on stable doses of L-DOPA/carbidopa and selegiline. Levodopa 71-77 catechol-O-methyltransferase Homo sapiens 51-55 8635184-1 1995 Tolcapone, a catechol-O-methyltransferase inhibitor, can interfere with the metabolism of levodopa and dopamine and could prolong the motor effect induced by levodopa in parkinsonian patients. Levodopa 158-166 catechol-O-methyltransferase Homo sapiens 13-41 7952244-3 1994 Clinical studies show that COMT inhibitors prolong the action of levodopa in patients with the "wearing off" phenomenon. Levodopa 65-73 catechol-O-methyltransferase Homo sapiens 27-31 7834959-8 1994 On the other hand, the metabolites of NA and DA by catechol-O-methyltransferase (COMT), normetanephrine (NMN) and 3-methoxytyramine (3-MT), decreased in the patients treated with droxidopa and L-DOPA compared with the patients administered with L-DOPA alone and control patients. Levodopa 193-199 catechol-O-methyltransferase Homo sapiens 81-85 7834959-8 1994 On the other hand, the metabolites of NA and DA by catechol-O-methyltransferase (COMT), normetanephrine (NMN) and 3-methoxytyramine (3-MT), decreased in the patients treated with droxidopa and L-DOPA compared with the patients administered with L-DOPA alone and control patients. Levodopa 245-251 catechol-O-methyltransferase Homo sapiens 81-85 7952244-6 1994 Thus, COMT inhibitors and clozapine provide new opportunities for the treatment of patients with longstanding PD and fluctuating responses to levodopa. Levodopa 142-150 catechol-O-methyltransferase Homo sapiens 6-10 8035323-1 1994 Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catecholamine and catechol drugs such as levodopa and methyldopa. Levodopa 108-116 catechol-O-methyltransferase Homo sapiens 0-28 8035323-1 1994 Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catecholamine and catechol drugs such as levodopa and methyldopa. Levodopa 108-116 catechol-O-methyltransferase Homo sapiens 30-34 8190296-0 1994 Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Levodopa 109-117 catechol-O-methyltransferase Homo sapiens 21-49 8190296-1 1994 Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. Levodopa 74-82 catechol-O-methyltransferase Homo sapiens 0-28 8190296-1 1994 Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. Levodopa 74-82 catechol-O-methyltransferase Homo sapiens 30-34 8190296-9 1994 We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa. Levodopa 84-92 catechol-O-methyltransferase Homo sapiens 31-35 8190296-9 1994 We conclude that inhibition of COMT by entacapone increases the plasma half-life of levodopa and augments the antiparkinsonian effects of single and repeated doses of levodopa. Levodopa 167-175 catechol-O-methyltransferase Homo sapiens 31-35 8127373-3 1994 COMT also inactivates catechol-type compounds such as L-DOPA. Levodopa 54-60 catechol-O-methyltransferase Homo sapiens 0-4 8126502-0 1994 Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson"s disease. Levodopa 130-138 catechol-O-methyltransferase Homo sapiens 44-72 27520516-6 1994 COMT inhibitors also decrease the levels of COMT-dependent metabolites of adrenaline (epinephrine) and noradrenaline (norepinephrine) in plasma.Entacapone, to1capone and CGP 28014 improve the bioavailability of levodopa and inhibit the formation of 3-0-methyldopa in human volunteers. Levodopa 211-219 catechol-O-methyltransferase Homo sapiens 0-4 27520516-6 1994 COMT inhibitors also decrease the levels of COMT-dependent metabolites of adrenaline (epinephrine) and noradrenaline (norepinephrine) in plasma.Entacapone, to1capone and CGP 28014 improve the bioavailability of levodopa and inhibit the formation of 3-0-methyldopa in human volunteers. Levodopa 211-219 catechol-O-methyltransferase Homo sapiens 44-48 8126502-1 1994 Catechol-O-methyltransferase (COMT) inhibitors may be useful in the treatment of Parkinson"s disease by improving the bioavailability of levodopa and by prolonging its effects. Levodopa 137-145 catechol-O-methyltransferase Homo sapiens 0-28 8126502-1 1994 Catechol-O-methyltransferase (COMT) inhibitors may be useful in the treatment of Parkinson"s disease by improving the bioavailability of levodopa and by prolonging its effects. Levodopa 137-145 catechol-O-methyltransferase Homo sapiens 30-34 8126502-5 1994 Plasma levodopa concentrations were increased with both doses of the COMT inhibitor. Levodopa 7-15 catechol-O-methyltransferase Homo sapiens 69-73 8070503-3 1994 High red blood cell (RBC) COMT activity has been correlated with a poor response to levodopa treatment in Parkinson"s disease. Levodopa 84-92 catechol-O-methyltransferase Homo sapiens 26-30 8255478-0 1993 Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Levodopa 58-66 catechol-O-methyltransferase Homo sapiens 0-28