PMID-sentid Pub_year Sent_text compound_name comp_offset prot_official_name organism prot_offset 22548395-7 2012 Tolcapone 1 muM was used to inhibit COMT. Tolcapone 0-9 latexin Homo sapiens 12-15 22548395-7 2012 Tolcapone 1 muM was used to inhibit COMT. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 36-40 22548395-10 2012 In Ha-Cat cells, COMT activity increased 24 h after a high dose UVB but decreased at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. Tolcapone 91-100 catechol-O-methyltransferase Homo sapiens 17-21 22108205-9 2012 CONCLUSIONS: HRR1 after 6MW test is a strong predictor of clinical worsening and TCW in patients with IPAH. Tolcapone 81-84 nuclear receptor subfamily 1 group H member 4 Homo sapiens 13-17 21846718-9 2011 Finally, we show that the COMT inhibitor tolcapone induces cell death via the mechanism of apoptosis, and its cytotoxicity is dependent on dosage and correlated with COMT Val/Met genotypes in human lymphoblastoid cells. Tolcapone 41-50 catechol-O-methyltransferase Homo sapiens 26-30 22364739-8 2012 Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 97-101 22364739-8 2012 Tolcapone had opposite effects in the two genotype groups: it worsened N-back performance in Met-COMT subjects but enhanced it in Val-COMT subjects. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 134-138 22364739-9 2012 Tolcapone made Met-COMT subjects less risk averse but Val-COMT subjects more so. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 19-23 22123108-2 2012 At the present time, tolcapone and entacapone are the only two COMT inhibitors available in the market. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 63-67 22860182-7 2012 Finally, novel non-nitrocatechol COMT inhibitors displayed less potent uncoupling of the mitochondrial membrane potential (MMP) compared to tolcapone as well as nonhepatotoxic entacapone, thus mitigating the risk of hepatotoxicity. Tolcapone 140-149 catechol-O-methyltransferase Homo sapiens 33-37 21999147-9 2011 The COMT activity inhibiting drugs including tolcapone and entacapone, have shown promising potential as they selectively modulate dopaminergic transmission. Tolcapone 45-54 catechol-O-methyltransferase Homo sapiens 4-8 21846718-9 2011 Finally, we show that the COMT inhibitor tolcapone induces cell death via the mechanism of apoptosis, and its cytotoxicity is dependent on dosage and correlated with COMT Val/Met genotypes in human lymphoblastoid cells. Tolcapone 41-50 catechol-O-methyltransferase Homo sapiens 166-170 21846718-10 2011 These results suggest that MB-COMT specific inhibitors can be developed and that tolcapone may be less hazardous at low doses and in specific genetic backgrounds. Tolcapone 81-90 catechol-O-methyltransferase Homo sapiens 30-34 21521027-4 2011 The potential role of the COMT inhibitor tolcapone to improve cognitive function in health and disease is also presented here. Tolcapone 41-50 catechol-O-methyltransferase Homo sapiens 26-30 21062636-0 2011 Kleptomania treated with tolcapone, a catechol-O-methyl-transferase (COMT) inhibitor. Tolcapone 25-34 catechol-O-methyltransferase Homo sapiens 38-67 21370258-10 2011 No differences between drugs within each class were observed other than the catechol-O-methyl transferase inhibitor tolcapone appearing more efficacious than entacapone. Tolcapone 116-125 catechol-O-methyltransferase Homo sapiens 76-105 21062636-0 2011 Kleptomania treated with tolcapone, a catechol-O-methyl-transferase (COMT) inhibitor. Tolcapone 25-34 catechol-O-methyltransferase Homo sapiens 69-73 20394182-1 2010 OBJECTIVE: To examine changes in quality of life (QOL) and global clinical status after 30 days of adjunctive treatment with tolcapone, a revers-ible inhibitor of catechol-O-methyltransferase, in patients with fluctuating Parkinson"s disease. Tolcapone 125-134 catechol-O-methyltransferase Homo sapiens 163-191 21845099-7 2011 The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified. Tolcapone 188-197 valyl-tRNA synthetase 1 Rattus norvegicus 9-14 21845099-7 2011 The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified. Tolcapone 188-197 valyl-tRNA synthetase 1 Rattus norvegicus 16-39 20870159-6 2010 RESULTS: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC(90) 5.3 +- 4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone 43-52 catechol-O-methyltransferase Rattus norvegicus 28-32 20870159-9 2010 CONCLUSIONS: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[(11)C]SKF 82957. Tolcapone 51-60 catechol-O-methyltransferase Rattus norvegicus 36-40 20150427-0 2010 Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity. Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 30-58 20150427-0 2010 Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity. Tolcapone 15-24 synuclein alpha Homo sapiens 97-112 20150427-5 2010 Here, we show that entacapone and tolcapone are potent inhibitors of alpha-syn and beta-amyloid (Abeta) oligomerization and fibrillogenesis, and they also protect against extracellular toxicity induced by the aggregation of both proteins. Tolcapone 34-43 synuclein alpha Homo sapiens 69-78 20150427-5 2010 Here, we show that entacapone and tolcapone are potent inhibitors of alpha-syn and beta-amyloid (Abeta) oligomerization and fibrillogenesis, and they also protect against extracellular toxicity induced by the aggregation of both proteins. Tolcapone 34-43 amyloid beta precursor protein Homo sapiens 97-102 20150427-7 2010 Our findings present the first characterization of the anti-amyloidogenic properties of tolcapone and entacapone against both alpha-synuclein and Abeta42 and highlight the potential of this class of nitro-catechol compounds as anti-amyloidogenic agents. Tolcapone 88-97 synuclein alpha Homo sapiens 126-141 20502133-0 2010 Replacing a dopamine agonist by the COMT-inhibitor tolcapone as an adjunct to L-dopa in the treatment of Parkinson"s disease: a randomized, multicenter, open-label, parallel-group study. Tolcapone 51-60 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. Tolcapone 76-85 catechol-O-methyltransferase Homo sapiens 45-49 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. Tolcapone 76-85 catechol-O-methyltransferase Homo sapiens 189-193 18536698-0 2008 Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism. Tolcapone 80-89 catechol-O-methyltransferase Homo sapiens 101-105 19783845-3 2010 Tolcapone and entacapone are potent inhibitors of catechol-O-methyltransferase (COMT) for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 50-78 19783845-3 2010 Tolcapone and entacapone are potent inhibitors of catechol-O-methyltransferase (COMT) for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 80-84 19615953-0 2009 Identification of metabolite profiles of the catechol-O-methyl transferase inhibitor tolcapone in rat urine using LC/MS-based metabonomics analysis. Tolcapone 85-94 catechol-O-methyltransferase Rattus norvegicus 45-74 19615953-3 2009 A method using mass spectrometry-based metabonomics combined with multivariate statistical analysis was applied to rapidly identify metabolite profiles of tolcapone, a catechol-O-methyl transferase inhibitor for Parkinson"s disease treatment. Tolcapone 155-164 catechol-O-methyltransferase Rattus norvegicus 168-197 18536698-0 2008 Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism. Tolcapone 80-89 catechol-O-methyltransferase Homo sapiens 65-69 21095464-1 2010 Entacapone and tolcapone are reversible COMT inhibitors which have been approved for clinical use in patients with Parkinson disease (PD). Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 40-44 21095464-6 2010 Tolcapone is longer acting and more potent COMT inhibitor than entacapone; nebicapone lies in between. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 43-47 19699472-0 2009 Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase rs4818c/g polymorphism. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 83-111 19699472-1 2009 BACKGROUND: The functional catechol-O-methyltransferase (COMT) valine158methionine (val158met) polymorphism determines prepulse inhibition (PPI) levels and working memory performance and the effects of tolcapone on these functions. Tolcapone 202-211 catechol-O-methyltransferase Homo sapiens 57-61 19503773-3 2009 In the last 10 years, the catechol-O-methyltransferase (COMT) inhibitor tolcapone has been studied for its efficacy as an adjunctive treatment to levodopa plus a dopa decarboxylase inhibitor. Tolcapone 72-81 catechol-O-methyltransferase Homo sapiens 26-54 19503773-3 2009 In the last 10 years, the catechol-O-methyltransferase (COMT) inhibitor tolcapone has been studied for its efficacy as an adjunctive treatment to levodopa plus a dopa decarboxylase inhibitor. Tolcapone 72-81 catechol-O-methyltransferase Homo sapiens 56-60 19503773-3 2009 In the last 10 years, the catechol-O-methyltransferase (COMT) inhibitor tolcapone has been studied for its efficacy as an adjunctive treatment to levodopa plus a dopa decarboxylase inhibitor. Tolcapone 72-81 dopa decarboxylase Homo sapiens 162-180 18854987-3 2009 As such, the beneficial cognitive effects of the COMT inhibitor tolcapone are postulated to be the result of increased bioavailability of DA in the PFC. Tolcapone 64-73 catechol-O-methyltransferase Rattus norvegicus 49-53 18536698-11 2008 Enhancement of PFC DA signaling with tolcapone improves both PPI and working memory in a COMT Val158Met genotype-specific manner. Tolcapone 37-46 catechol-O-methyltransferase Homo sapiens 89-93 17705259-6 2007 Therefore, the capacity of three catechol-O-methyltransferase (COMT) inhibitors, entacapone, nitecapone, and tolcapone to protect ALP from oxidative damage was also investigated and found to be very similar to the most potent reference antioxidants. Tolcapone 109-118 alkaline phosphatase, placental Homo sapiens 130-133 18394561-7 2008 The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Tolcapone 19-28 catechol-O-methyltransferase Homo sapiens 4-8 18728767-0 2008 COMT inhibition with tolcapone in the treatment algorithm of patients with Parkinson"s disease (PD): relevance for motor and non-motor features. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 0-4 18728767-2 2008 Tolcapone is a potent COMT inhibitor whose utilization in PD is limited due to safety concerns on liver toxicity. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 22-26 18728767-6 2008 We propose that future guidelines include a trial with tolcapone in all PD patients who continue to complain about motor fluctuations despite treatment with entacapone and/or MAO-B inhibitors. Tolcapone 55-64 monoamine oxidase B Homo sapiens 175-180 18052761-4 2007 Tolcapone and entacapone are selective and potent COMT inhibitors that slow the metabolism of levodopa, thus prolonging its effects. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 50-54 18052761-5 2007 While both drugs act peripherally, tolcapone also inhibits COMT in the CNS. Tolcapone 35-44 catechol-O-methyltransferase Homo sapiens 59-63 17909307-1 2007 Tolcapone (Tasmar), an inhibitor of catechol-O-methyltransferase, is an effective antiparkinsonian agent when used as an adjunct to levodopa in patients with Parkinson disease who have end-of-dose motor fluctuations. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 36-64 17573159-9 2007 Inhibition of catechol-O-methyltransferase activity by tolcapone or entacapone did not increase lipopolysaccharide-induced neurotoxicity. Tolcapone 55-64 catechol-O-methyltransferase Homo sapiens 14-42 16758261-5 2006 Blood samples were taken before and after 2 days of additional application of the centrally acting catechol-O-methyltransferase inhibitor tolcapone 100 mg t.i.d. Tolcapone 138-147 catechol-O-methyltransferase Homo sapiens 99-127 17059382-2 2006 Tolcapone is a catechol-O-methyltransferase inhibitor that extends the action of levodopa. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 15-43 17063156-4 2007 To explore in a proof of concept study the effects of tolcapone, a CNS penetrant specific COMT inhibitor, we performed a randomized, double blind, placebo controlled, and crossover design of this drug in normal subjects stratified by COMT (val158met) genotype. Tolcapone 54-63 catechol-O-methyltransferase Homo sapiens 90-94 17579498-7 2007 One strategy consists of the use of CNS-penetrant COMT inhibitors such as tolcapone. Tolcapone 74-83 catechol-O-methyltransferase Homo sapiens 50-54 17630819-11 2007 Therefore, agents that block COMT, such as tolcapone and entacapone, increase the elimination half-life of levodopa. Tolcapone 43-52 catechol-O-methyltransferase Homo sapiens 29-33 16758261-9 2006 CONCLUSION: Our prospective trial shows, that COMT inhibition with tolcapone lowers tHcy synthesis. Tolcapone 67-76 catechol-O-methyltransferase Homo sapiens 46-50 16604736-4 2006 (2) Tolcapone, another COMT inhibitor, is back on the French market after being withdrawn because of serious hepatic effects. Tolcapone 4-13 catechol-O-methyltransferase Homo sapiens 23-27 15784340-1 2005 Aqueous solubility, apparent partition coefficient (logPapp) and catechol-O-methyltransferase (COMT, EC 2.1.1.6) inhibiting potency of entacapone and tolcapone were compared in vitro. Tolcapone 150-159 catechol-O-methyltransferase Rattus norvegicus 65-93 18046910-4 2006 Tolcapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor, shown to have both peripheral and central effects. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 37-65 18046910-4 2006 Tolcapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor, shown to have both peripheral and central effects. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 67-71 16355307-0 2005 [Comparison of the safety of the medicinal product in the European Union and the United States, tolcapone (Tasmar) -- COMT inhibitor as the analyzed example]. Tolcapone 96-105 catechol-O-methyltransferase Homo sapiens 118-122 15784340-1 2005 Aqueous solubility, apparent partition coefficient (logPapp) and catechol-O-methyltransferase (COMT, EC 2.1.1.6) inhibiting potency of entacapone and tolcapone were compared in vitro. Tolcapone 150-159 catechol-O-methyltransferase Rattus norvegicus 95-99 15784340-6 2005 Entacapone and tolcapone inhibited equally rat striatal COMT in vitro with Ki values of 1.86 and 2.50 nM, respectively. Tolcapone 15-24 catechol-O-methyltransferase Rattus norvegicus 56-60 15784340-10 2005 In conclusion, entacapone and tolcapone are equally potent COMT inhibitors against rat striatal COMT in vitro. Tolcapone 30-39 catechol-O-methyltransferase Rattus norvegicus 59-63 15784340-10 2005 In conclusion, entacapone and tolcapone are equally potent COMT inhibitors against rat striatal COMT in vitro. Tolcapone 30-39 catechol-O-methyltransferase Rattus norvegicus 96-100 15697329-1 2005 Tolcapone (Tasmar) is a selective, reversible inhibitor of peripheral and central catechol-O-methyltransferase (COMT). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 82-110 15697329-1 2005 Tolcapone (Tasmar) is a selective, reversible inhibitor of peripheral and central catechol-O-methyltransferase (COMT). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 112-116 15190105-2 2004 This study investigated the effect of tolcapone, a brain-penetrant COMT inhibitor, on a rat model of attentional set shifting, which is dependent on catecholamines and the medial PFC (mPFC). Tolcapone 38-47 catechol-O-methyltransferase Rattus norvegicus 67-71 15709899-12 2005 It is concluded that tolcapone can be safely used in Parkinsonian patients who do not respond or cannot, for other reasons, be prescribed with other COMT inhibitors. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 149-153 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). Tolcapone 68-77 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). Tolcapone 68-77 catechol-O-methyltransferase Homo sapiens 35-39 12898346-1 2003 We compared--retrospectively--the effects of a 3-month therapy with catechol- O-methyltransferase (COMT) inhibitors tolcapone (100 mg, t.i.d.) Tolcapone 116-125 catechol-O-methyltransferase Homo sapiens 68-97 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). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 29-57 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). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 59-63 12898346-1 2003 We compared--retrospectively--the effects of a 3-month therapy with catechol- O-methyltransferase (COMT) inhibitors tolcapone (100 mg, t.i.d.) Tolcapone 116-125 catechol-O-methyltransferase Homo sapiens 99-103 12573869-1 2003 Tolcapone is a mixed (peripheral and central) catechol-O-methyltransferase (COMT) inhibitor, whereas entacapone is a preferential peripheral COMT inhibitor. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 46-74 12884403-2 2003 Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt-gene-disrupted mice were studied at the age of 12 months. Tolcapone 172-181 catechol-O-methyltransferase Homo sapiens 155-159 12584150-6 2003 We propose a plausible explanation for the paradoxical in vivo regioselectivity of O-methylation of BIA 3-202, as well as of its related COMT inhibitor tolcapone. Tolcapone 152-161 catechol-O-methyltransferase Homo sapiens 137-141 12538800-1 2003 Two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone, were compared in the rat to elucidate the actual differences between their pharmacokinetics and pharmacodynamics after single and repeated administration. Tolcapone 67-76 catechol-O-methyltransferase Rattus norvegicus 34-38 12538800-5 2003 After a single oral dose (10 mg/kg), both entacapone and tolcapone produced an equal maximal degree of COMT inhibition in peripheral tissues, but tolcapone inhibited striatal COMT more effectively than did entacapone. Tolcapone 57-66 catechol-O-methyltransferase Rattus norvegicus 103-107 12538800-5 2003 After a single oral dose (10 mg/kg), both entacapone and tolcapone produced an equal maximal degree of COMT inhibition in peripheral tissues, but tolcapone inhibited striatal COMT more effectively than did entacapone. Tolcapone 146-155 catechol-O-methyltransferase Rattus norvegicus 175-179 12538800-7 2003 In tolcapone-treated animals, there was still extensive COMT inhibition present in peripheral tissues, and the degree of inhibition was higher than that attained after a single dose. Tolcapone 3-12 catechol-O-methyltransferase Rattus norvegicus 56-60 12538800-8 2003 The pharmacokinetic-pharmacodynamic modeling revealed that a plateau of COMT inhibition near the maximal attainable inhibition was reached already by plasma concentrations below 2000 ng/ml, both with entacapone and tolcapone. Tolcapone 215-224 catechol-O-methyltransferase Rattus norvegicus 72-76 12538800-9 2003 Entacapone and tolcapone inhibited equally rat liver COMT in vitro with K(i) values of 10.7 and 10.0 nM, respectively. Tolcapone 15-24 catechol-O-methyltransferase Rattus norvegicus 53-57 12538800-11 2003 The results also suggest that peripheral COMT is inhibited continuously when tolcapone is dosed at 12-h intervals, but this was not seen with entacapone. Tolcapone 77-86 catechol-O-methyltransferase Rattus norvegicus 41-45 12830929-4 2003 Such drugs include the catechol-O-methyl-transferase (COMT) inhibitors, such as tolcapone and entecapone, and new dopamine (DA) agonists with long half lives such as cabergoline, pramipexole or ropirinole. Tolcapone 80-89 catechol-O-methyltransferase Homo sapiens 54-58 12957500-4 2003 Oral administration of the COMT inhibitor tolcapone (2 doses of 15 mg/kg each with a 4-h interval) significantly reduced enzyme activity in the monkey brain. Tolcapone 42-51 catechol-O-methyltransferase Homo sapiens 27-31 12957500-6 2003 Importantly, however, COMT inhibition greatly magnified the differences in CSF DOPAC levels between control and parkinsonian monkeys, since MPTP-induced DOPAC depletion was 35% in the absence vs >60% in the presence of tolcapone. Tolcapone 219-228 catechol-O-methyltransferase Homo sapiens 22-26 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). Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 39-67 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). Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 69-73 12588182-1 2003 Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor used for control of motor fluctuations in Parkinson"s disease (PD). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 15-43 12588182-1 2003 Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor used for control of motor fluctuations in Parkinson"s disease (PD). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 45-49 12573869-1 2003 Tolcapone is a mixed (peripheral and central) catechol-O-methyltransferase (COMT) inhibitor, whereas entacapone is a preferential peripheral COMT inhibitor. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 76-80 12573869-3 2003 Tolcapone may also impair the extraneuronal catabolism of DA by inhibiting COMT activity in the brain. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 75-79 12573869-5 2003 Tolcapone and entacapone, at the dose of 15 mg/kg p.o., were almost equally effective in inhibiting COMT activity in duodenum and liver. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 100-104 12573869-6 2003 Tolcapone decreased striatal extracellular levels of homovanillic acid (HVA), thus confirming its central COMT inhibitory effect, whereas entacapone did not alter HVA efflux. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 106-110 12454735-1 2002 The toxicity profiles of entacapone and tolcapone, novel catechol- O-methyl-transferase (COMT) inhibitors, have been reported to differ from each other. Tolcapone 40-49 catechol-O-methyltransferase Rattus norvegicus 57-87 12393055-1 2002 Catechol-O-methyl transferase (COMT) inhibitors, entacapone and tolcapone, are used as an adjunctive treatment to L-dopa in Parkinson"s disease. Tolcapone 64-73 catechol-O-methyltransferase Rattus norvegicus 0-29 12393055-1 2002 Catechol-O-methyl transferase (COMT) inhibitors, entacapone and tolcapone, are used as an adjunctive treatment to L-dopa in Parkinson"s disease. Tolcapone 64-73 catechol-O-methyltransferase Rattus norvegicus 31-35 12454735-1 2002 The toxicity profiles of entacapone and tolcapone, novel catechol- O-methyl-transferase (COMT) inhibitors, have been reported to differ from each other. Tolcapone 40-49 catechol-O-methyltransferase Rattus norvegicus 89-93 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. Tolcapone 78-87 catechol-O-methyltransferase Homo sapiens 61-65 12180806-1 2002 Entacapone and tolcapone, novel catechol-O-methyl-transferase (COMT) inhibitors, have been developed for the treatment of Parkinson"s disease in combination with levodopa. Tolcapone 15-24 catechol-O-methyltransferase Rattus norvegicus 32-61 12180806-1 2002 Entacapone and tolcapone, novel catechol-O-methyl-transferase (COMT) inhibitors, have been developed for the treatment of Parkinson"s disease in combination with levodopa. Tolcapone 15-24 catechol-O-methyltransferase Rattus norvegicus 63-67 12111468-0 2002 Different modes of action of catecholamine-O-methyltransferase inhibitors entacapone and tolcapone on adenylyl cyclase activity in vitro. Tolcapone 89-98 catechol-O-methyltransferase Rattus norvegicus 29-62 12111468-1 2002 Catechol-O-methyltransferase (COMT) inhibitors such as entacapone and tolcapone are used as adjuncts to L-DOPA ( l-3,4-dihydroxyphenylalanine, levodopa) in the treatment of Parkinson"s disease. Tolcapone 70-79 catechol-O-methyltransferase Rattus norvegicus 0-28 12111468-1 2002 Catechol-O-methyltransferase (COMT) inhibitors such as entacapone and tolcapone are used as adjuncts to L-DOPA ( l-3,4-dihydroxyphenylalanine, levodopa) in the treatment of Parkinson"s disease. Tolcapone 70-79 catechol-O-methyltransferase Rattus norvegicus 30-34 11942697-2 2002 Inhibition of catechol O-methyltransferase (COMT) with tolcapone led to increases in extracellular dopamine levels only when the baseline dopamine level was elevated by administration of L-3,4-dihydroxyphenylalanine in combination with the decarboxylation inhibitor carbidopa. Tolcapone 55-64 catechol-O-methyltransferase Rattus norvegicus 14-42 11942697-2 2002 Inhibition of catechol O-methyltransferase (COMT) with tolcapone led to increases in extracellular dopamine levels only when the baseline dopamine level was elevated by administration of L-3,4-dihydroxyphenylalanine in combination with the decarboxylation inhibitor carbidopa. Tolcapone 55-64 catechol-O-methyltransferase Rattus norvegicus 44-48 11942697-3 2002 Increases in dopamine levels in striatal dialysates by blockade of reuptake were enhanced by inhibition of metabolic degradation of dopamine by tolcapone, a selective catechol O-methyltransferase inhibitor. Tolcapone 144-153 catechol-O-methyltransferase Rattus norvegicus 167-195 11793426-0 2002 18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson"s disease. Tolcapone 27-36 catechol-O-methyltransferase Homo sapiens 55-59 11793426-1 2002 Tolcapone is a potent, selective, and reversible inhibitor of cathecol-O-methyl-transferase (COMT). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 62-91 11793426-1 2002 Tolcapone is a potent, selective, and reversible inhibitor of cathecol-O-methyl-transferase (COMT). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 93-97 11793426-3 2002 Tolcapone"s ability to inhibit central COMT in humans at therapeutic concentrations is not yet clear. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 39-43 11793426-4 2002 The aim was to determine the effect of tolcapone on central COMT activity in Parkinson"s disease (PD) using (18)F-dopa positron emission tomography (PET). Tolcapone 39-48 catechol-O-methyltransferase Homo sapiens 60-64 11793426-13 2002 These findings are compatible with clinical doses of tolcapone having a significant blocking effect on peripheral and central COMT but not DDC activity in PD. Tolcapone 53-62 catechol-O-methyltransferase Homo sapiens 126-130 11586115-2 2001 Tolcapone and entacapone are two currently available catechol- O -methyltransferase inhibitors that have demonstrated efficacy in the treatment of advanced PD. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 53-83 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. Tolcapone 35-44 catechol-O-methyltransferase Homo sapiens 4-8 11806720-3 2002 Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). Tolcapone 223-232 catechol-O-methyltransferase Rattus norvegicus 156-160 11248589-9 2001 Since adrenergic stimulation may increase the hepatotoxic potential of commonly used drugs, usually thought of as safe for the liver, we postulate that some of the already reported life threatening complications of tolcapone could be related to excessive adrenergic stimulation by high catecholamine levels caused by inhibition of COMT activity. Tolcapone 215-224 catechol-O-methyltransferase Homo sapiens 331-335 11489299-4 2001 Tolcapone, a selective catechol-O-methyltransferase inhibitor, was used as a positive reference compound. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 23-51 11318939-1 2001 BACKGROUND: In recent years, several nitrocatechol derivatives (tolcapone, entacapone, and nitecapone) have been developed and found to be highly selective and potent inhibitors of catechol-O-methyltransferase (COMT). Tolcapone 64-73 catechol-O-methyltransferase Rattus norvegicus 181-209 11318939-1 2001 BACKGROUND: In recent years, several nitrocatechol derivatives (tolcapone, entacapone, and nitecapone) have been developed and found to be highly selective and potent inhibitors of catechol-O-methyltransferase (COMT). Tolcapone 64-73 catechol-O-methyltransferase Rattus norvegicus 211-215 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. Tolcapone 0-9 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. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 49-53 11261749-1 2001 Entacapone and tolcapone are novel COMT (catechol-O-methyltransferase) inhibitors indicated for the adjunctive treatment of Parkinson"s disease (PD) in combination with levodopa. Tolcapone 15-24 catechol-O-methyltransferase Rattus norvegicus 35-39 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. Tolcapone 113-122 catechol-O-methyltransferase Homo sapiens 82-86 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. Tolcapone 107-116 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. Tolcapone 107-116 catechol-O-methyltransferase Homo sapiens 91-95 11290879-11 2001 Additional tolcapone reversed the protective effect of COMT. Tolcapone 11-20 catechol-O-methyltransferase Homo sapiens 55-59 11261749-9 2001 We conclude that the toxicological profile of the two COMT inhibitors, entacapone and tolcapone, differ from each other, tolcapone--unlike entacapone--showed hepatotoxicity. Tolcapone 121-130 catechol-O-methyltransferase Rattus norvegicus 54-58 11261749-1 2001 Entacapone and tolcapone are novel COMT (catechol-O-methyltransferase) inhibitors indicated for the adjunctive treatment of Parkinson"s disease (PD) in combination with levodopa. Tolcapone 15-24 catechol-O-methyltransferase Rattus norvegicus 41-69 11314772-0 2001 The central catechol-O-methyltransferase inhibitor tolcapone increases striatal hydroxyl radical production in L-DOPA/carbidopa treated rats. Tolcapone 51-60 catechol-O-methyltransferase Rattus norvegicus 12-40 11038168-10 2000 Entacapone showed a 3 to 4 times higher V(max) value and a 4 to 6 times lower K(m) value compared with those of tolcapone both in UGT1A9 cell lysates and in human liver microsomes. Tolcapone 112-121 UDP glucuronosyltransferase family 1 member A9 Homo sapiens 130-136 11038168-1 2000 The COMT inhibitors entacapone and tolcapone are rapidly metabolized in vivo, mainly by glucuronidation. Tolcapone 35-44 catechol-O-methyltransferase Homo sapiens 4-8 11038168-9 2000 The kinetic data illustrates that UGT1A9 exhibited a much greater rate of glucuronidation and a far lower K(m) value for both entacapone and tolcapone than UGT2B15 and UGT2B7 whose contribution is minor by comparison. Tolcapone 141-150 UDP glucuronosyltransferase family 1 member A9 Homo sapiens 34-40 10806608-1 2000 To assess the effect of tolcapone (an inhibitor of cytochrome P450 [CYP] 2C9 in vitro) on the pharmacokinetics and hypoglycemic effect of the CYP 2C9 substrate tolbutamide, 12 healthy male volunteers were randomized to receive a single dose of tolbutamide 500 mg plus either placebo or tolcapone 200 mg after an overnight fast and 30 minutes after the start of a 6.5-hour 5% glucose infusion (150 mL/h). Tolcapone 24-33 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 142-149 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. Tolcapone 30-39 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. Tolcapone 30-39 catechol-O-methyltransferase Homo sapiens 92-96 10900399-2 2000 Tolcapone was the first COMT inhibitor available for use as adjunctive therapy to levodopa in Parkinson"s disease (PD). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 24-28 11081220-1 2000 Inhibition of catechol-0-methyltransferase (COMT) activity by Tolcapone was shown to result in increase of the striatal DA extracellular content in unrestrained rats pretreated with L-3,4-dihydroxyphenilalanine combined with Carbidopa, the decarboxylation inhibiting agent. Tolcapone 62-71 catechol-O-methyltransferase Rattus norvegicus 14-42 11081220-1 2000 Inhibition of catechol-0-methyltransferase (COMT) activity by Tolcapone was shown to result in increase of the striatal DA extracellular content in unrestrained rats pretreated with L-3,4-dihydroxyphenilalanine combined with Carbidopa, the decarboxylation inhibiting agent. Tolcapone 62-71 catechol-O-methyltransferase Rattus norvegicus 44-48 10882160-2 2000 Entacapone and tolcapone are new potent, selective and reversible nitrocatechol-type COMT inhibitors. Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 85-89 10882160-4 2000 In human volunteers, both entacapone and tolcapone dose-dependently inhibit the COMT activity in erythrocytes, improve the bioavailability and decrease the elimination of levodopa, and inhibit the formation of 3-O-methyldopa (3-OMD). Tolcapone 41-50 catechol-O-methyltransferase Homo sapiens 80-84 10770481-0 2000 Update on "open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder". Tolcapone 68-77 catechol-O-methyltransferase Homo sapiens 29-57 10895397-0 2000 The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson"s disease. Tolcapone 73-82 catechol-O-methyltransferase Homo sapiens 25-29 10895397-0 2000 The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson"s disease. Tolcapone 73-82 catechol-O-methyltransferase Homo sapiens 86-90 10895397-1 2000 Patients with Parkinson"s Disease (PD) have a variable response to tolcapone, a catechol-O-methyltransferase (COMT) inhibitor. Tolcapone 67-76 catechol-O-methyltransferase Homo sapiens 80-108 10895397-1 2000 Patients with Parkinson"s Disease (PD) have a variable response to tolcapone, a catechol-O-methyltransferase (COMT) inhibitor. Tolcapone 67-76 catechol-O-methyltransferase Homo sapiens 110-114 10803800-2 2000 Tolcapone withdrawal caused a transient elevation in COMT activity by 64% in patients receiving 100 mg three times daily and by 128% in those receiving 200 mg three times daily at approximately 1-2 weeks after discontinuation of drug. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 53-57 10606836-1 2000 AIMS: To use pharmacostatistical models to characterize tolcapone"s pharmacokinetics in parkinsonian patients, and to identify any demographic subpopulations which may be at risk of either under- or over-exposure to this catechol-O-methyltransferase (COMT) inhibitor. Tolcapone 56-65 catechol-O-methyltransferase Homo sapiens 221-249 10692500-6 2000 OR-486 and the clinically used COMT inhibitor tolcapone showed similar effects. Tolcapone 46-55 catechol-O-methyltransferase Homo sapiens 31-35 10703007-2 2000 Registration of the inhibitor of the catechol-O-methyltransfersase (COMT) tolcapone has been stopped due to the possible relationship of tolcapone treatment to three cases of fatal hepatitis. Tolcapone 74-83 catechol-O-methyltransferase Homo sapiens 37-66 10703007-2 2000 Registration of the inhibitor of the catechol-O-methyltransfersase (COMT) tolcapone has been stopped due to the possible relationship of tolcapone treatment to three cases of fatal hepatitis. Tolcapone 74-83 catechol-O-methyltransferase Homo sapiens 68-72 10703007-2 2000 Registration of the inhibitor of the catechol-O-methyltransfersase (COMT) tolcapone has been stopped due to the possible relationship of tolcapone treatment to three cases of fatal hepatitis. Tolcapone 137-146 catechol-O-methyltransferase Homo sapiens 37-66 10703007-2 2000 Registration of the inhibitor of the catechol-O-methyltransfersase (COMT) tolcapone has been stopped due to the possible relationship of tolcapone treatment to three cases of fatal hepatitis. Tolcapone 137-146 catechol-O-methyltransferase Homo sapiens 68-72 10606836-1 2000 AIMS: To use pharmacostatistical models to characterize tolcapone"s pharmacokinetics in parkinsonian patients, and to identify any demographic subpopulations which may be at risk of either under- or over-exposure to this catechol-O-methyltransferase (COMT) inhibitor. Tolcapone 56-65 catechol-O-methyltransferase Homo sapiens 251-255 10733264-12 2000 Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, producing a 47% reduction in "off" time. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 36-40 10565698-2 1999 Tolcapone is the first drug brought to market from the new class of selective and reversible inhibitors of catechol-O-methyltransferase. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 107-135 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. Tolcapone 56-65 catechol-O-methyltransferase Homo sapiens 18-47 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. Tolcapone 56-65 catechol-O-methyltransferase Homo sapiens 49-53 11147512-2 2000 Two COMT inhibitors, tolcapone and entacapone, have recently been made available as adjunctive agents to levodopa. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 4-8 10619191-1 1999 The cerebral availability of the peripherally and centrally acting catechol-O-methyltransferase (COMT) inhibitor tolcapone is not known in humans. Tolcapone 113-122 catechol-O-methyltransferase Homo sapiens 67-95 10619191-1 1999 The cerebral availability of the peripherally and centrally acting catechol-O-methyltransferase (COMT) inhibitor tolcapone is not known in humans. Tolcapone 113-122 catechol-O-methyltransferase Homo sapiens 97-101 10619191-5 1999 Thus, tolcapone efficiently inhibits COMT after crossing the blood-brain barrier in humans. Tolcapone 6-15 catechol-O-methyltransferase Homo sapiens 37-41 10490706-8 1999 These provisional findings suggest that newly developed COMT inhibitors such as tolcapone, applied in Parkinson"s disease, might in due time be considered in the treatment of ADHD. Tolcapone 80-89 catechol-O-methyltransferase Homo sapiens 56-60 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. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 4-8 11147508-2 2000 This paper examines the pharmacology of COMT inhibitors such as tolcapone and entacapone, and considers the effects of these drugs on the pharmacolinetics of levodopa. Tolcapone 64-73 catechol-O-methyltransferase Homo sapiens 40-44 11147510-1 2000 This paper reviews the issue of hepatotoxicity with the use of the catechol-O-methly transferase (COMT) inhibitors tolcapone and entacapone. Tolcapone 115-124 catechol-O-methyltransferase Homo sapiens 67-96 11147510-1 2000 This paper reviews the issue of hepatotoxicity with the use of the catechol-O-methly transferase (COMT) inhibitors tolcapone and entacapone. Tolcapone 115-124 catechol-O-methyltransferase Homo sapiens 98-102 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. Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 67-71 10407949-4 1999 Severe side effects have been mentioned in connection with the COMT inhibitor tolcapone in recent months. Tolcapone 78-87 catechol-O-methyltransferase Homo sapiens 63-67 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. Tolcapone 6-15 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. Tolcapone 6-15 catechol-O-methyltransferase Homo sapiens 57-61 10510160-8 1999 During tolcapone treatment these values were on average 0.35 microg ml-1 h (AUC(0,tau), week 1-2), 0. Tolcapone 7-16 microtubule associated protein tau Homo sapiens 82-85 10451758-1 1999 The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson"s medications. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 4-8 10440460-0 1999 Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. Tolcapone 57-66 catechol-O-methyltransferase Homo sapiens 18-46 10440460-1 1999 Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 15-43 10440460-1 1999 Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 45-49 10448949-0 1999 Determination of the catechol-O-methyltransferase inhibitor tolcapone and three of its metabolites in animal and human plasma and urine by reversed-phase high-performance liquid chromatography with ultraviolet detection. Tolcapone 60-69 catechol-O-methyltransferase Homo sapiens 21-49 10064789-11 1999 In the liver, 0.3 mg/kg tolcapone resulted in 82% inhibition of MB-COMT and 31% inhibition of S-COMT. Tolcapone 24-33 catechol-O-methyltransferase Homo sapiens 67-71 10323260-0 1999 Effect of tolcapone, a catechol-O-methyltransferase inhibitor, on striatal dopaminergic transmission during blockade of dopamine uptake. Tolcapone 10-19 catechol-O-methyltransferase Rattus norvegicus 23-51 10323260-2 1999 Using microdialysis in freely moving rats, it was determined that combined administration of tolcapone with GBR 12909 resulted in a further increase of dopamine levels over that obtained without the catechol-O-methyltransferase inhibitor, while tolcapone alone failed to change dopamine levels. Tolcapone 93-102 catechol-O-methyltransferase Rattus norvegicus 199-227 10053234-1 1999 This study investigated the potential interaction between tolcapone, a catechol-O-methyltransferase (COMT) inhibitor, and the decarboxylase inhibitor, benserazide. Tolcapone 58-67 catechol-O-methyltransferase Homo sapiens 71-99 10053234-1 1999 This study investigated the potential interaction between tolcapone, a catechol-O-methyltransferase (COMT) inhibitor, and the decarboxylase inhibitor, benserazide. Tolcapone 58-67 catechol-O-methyltransferase Homo sapiens 101-105 10064789-1 1999 The present study was aimed to evaluate the sensitivity of soluble (S) and membrane bound (MB) catechol-O-methyltransferase (COMT) from rat brain and liver to inhibitors which interact with the enzyme as competitive (tropolone), non-competitive (S-adenosyl-l-homocysteine; SAHC) and tight-binding (tolcapone and 3,5-dinitrocatechol) inhibitors. Tolcapone 298-307 catechol-O-methyltransferase Rattus norvegicus 125-129 10064789-11 1999 In the liver, 0.3 mg/kg tolcapone resulted in 82% inhibition of MB-COMT and 31% inhibition of S-COMT. Tolcapone 24-33 catechol-O-methyltransferase Homo sapiens 96-100 10064789-3 1999 When using a fixed amount of total protein (2 micrograms/ml), but variable concentrations of COMT, the inhibitory potency of tolcapone upon S- and MB-COMT activity in the brain was in the low nM range (IC50"s of 2 and 3 nM, respectively), whereas in liver the IC50 values for tolcapone against liver MB- and S-COMT (IC50"s of 123 and 795 nM, respectively) were markedly higher than those observed in the brain. Tolcapone 125-134 catechol-O-methyltransferase Homo sapiens 93-97 10064789-3 1999 When using a fixed amount of total protein (2 micrograms/ml), but variable concentrations of COMT, the inhibitory potency of tolcapone upon S- and MB-COMT activity in the brain was in the low nM range (IC50"s of 2 and 3 nM, respectively), whereas in liver the IC50 values for tolcapone against liver MB- and S-COMT (IC50"s of 123 and 795 nM, respectively) were markedly higher than those observed in the brain. Tolcapone 125-134 catechol-O-methyltransferase Homo sapiens 150-154 10064789-3 1999 When using a fixed amount of total protein (2 micrograms/ml), but variable concentrations of COMT, the inhibitory potency of tolcapone upon S- and MB-COMT activity in the brain was in the low nM range (IC50"s of 2 and 3 nM, respectively), whereas in liver the IC50 values for tolcapone against liver MB- and S-COMT (IC50"s of 123 and 795 nM, respectively) were markedly higher than those observed in the brain. Tolcapone 125-134 catechol-O-methyltransferase Homo sapiens 150-154 10064789-4 1999 By contrast, when inhibition studies were performed with a fixed concentration of COMT (15 nM), as determined by the Ackermann-Potter equation, tolcapone was found to be endowed with the same potency (in the low nM range) in inhibiting S- and MB-COMT from both brain and liver. Tolcapone 144-153 catechol-O-methyltransferase Homo sapiens 82-86 10064789-4 1999 By contrast, when inhibition studies were performed with a fixed concentration of COMT (15 nM), as determined by the Ackermann-Potter equation, tolcapone was found to be endowed with the same potency (in the low nM range) in inhibiting S- and MB-COMT from both brain and liver. Tolcapone 144-153 catechol-O-methyltransferase Homo sapiens 246-250 10064789-6 1999 Tropolone, a competitive inhibitor, was much less potent than tolcapone and 3,5-dinitrocatechol in inhibiting S- and MB-COMT from both brain and liver and its potency was found not to depend on enzyme concentration. Tolcapone 62-71 catechol-O-methyltransferase Homo sapiens 120-124 10064789-12 1999 In the brain, 3.0 mg/kg tolcapone inhibited 78% MB-COMT, whereas S-COMT activity was reduced by 38% only. Tolcapone 24-33 catechol-O-methyltransferase Homo sapiens 51-55 10064789-13 1999 In conclusion, the results reported here show that tolcapone is particularly potent in inhibiting MB-COMT from liver and brain under in vivo experimental conditions, though it does not discriminate between MB- and S-COMT under in vitro experimental conditions when using the same amount of enzyme in the assay. Tolcapone 51-60 catechol-O-methyltransferase Homo sapiens 101-105 10343151-0 1999 COMT inhibition by tolcapone further improves levodopa pharmacokinetics when combined with a dual-release formulation of levodopa/benserazide. Tolcapone 19-28 catechol-O-methyltransferase Homo sapiens 0-4 10064789-10 1999 One hour after its oral administration, tolcapone (0.3 to 30 mg/kg) was found to be much more potent against MB-COMT than against S-COMT. Tolcapone 40-49 catechol-O-methyltransferase Homo sapiens 112-116 10064789-10 1999 One hour after its oral administration, tolcapone (0.3 to 30 mg/kg) was found to be much more potent against MB-COMT than against S-COMT. Tolcapone 40-49 catechol-O-methyltransferase Homo sapiens 132-136 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). Tolcapone 131-140 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). Tolcapone 131-140 catechol-O-methyltransferase Homo sapiens 111-115 10651109-2 1999 Here we report that a treatment of the cerebral tissue with tolcapone, a central and peripheral inhibitor of COMT, does not change the membrane responses of midbrain dopamine neurons to dopamine and levodopa. Tolcapone 60-69 catechol-O-methyltransferase Rattus norvegicus 109-113 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. Tolcapone 0-9 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. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 66-70 10651109-4 1999 Therefore, the therapeutic action of tolcapone in Parkinson"s disease, might be dependent on the reduction of COMT activity in the extracerebral tissue. Tolcapone 37-46 catechol-O-methyltransferase Rattus norvegicus 110-114 9808337-1 1998 A new approach in the treatment of Parkinson"s disease is the inhibition of catechol-O-methyltransferase (COMT) with new generation COMT inhibitors, entacapone and tolcapone. Tolcapone 164-173 catechol-O-methyltransferase Homo sapiens 76-104 9917075-0 1999 Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 23-51 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. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 48-76 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. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 78-82 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. Tolcapone 0-9 dopa decarboxylase Homo sapiens 239-257 9918342-2 1999 The catechol-O-methyltransferase inhibitor tolcapone was compared with the dopamine agonist bromocriptine in an open-label, randomized trial involving 146 levodopa-treated parkinsonian patients with end-of-dose deterioration of efficacy. Tolcapone 43-52 catechol-O-methyltransferase Homo sapiens 4-32 9808337-1 1998 A new approach in the treatment of Parkinson"s disease is the inhibition of catechol-O-methyltransferase (COMT) with new generation COMT inhibitors, entacapone and tolcapone. Tolcapone 164-173 catechol-O-methyltransferase Homo sapiens 106-110 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. Tolcapone 97-106 catechol-O-methyltransferase Homo sapiens 58-86 9774242-3 1998 We wanted to determine whether the concentrations of free amine would be increased by catechol-O-methyltransferase inhibition with tolcapone and underpin the positive behavioural effects. Tolcapone 131-140 catechol-O-methyltransferase Rattus norvegicus 86-114 9754991-1 1998 OBJECTIVE: To evaluate fully the pharmacokinetics and pharmacodynamics of tolcapone, a novel inhibitor of catechol-O-methyltransferase (COMT), after oral and intravenous administration. Tolcapone 74-83 catechol-O-methyltransferase Homo sapiens 106-134 9724173-1 1998 Tolcapone (T) is a novel catechol-O-methyltransferase (COMT) inhibitor recently introduced for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Canis lupus familiaris 25-53 9724173-1 1998 Tolcapone (T) is a novel catechol-O-methyltransferase (COMT) inhibitor recently introduced for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Canis lupus familiaris 55-59 9754991-1 1998 OBJECTIVE: To evaluate fully the pharmacokinetics and pharmacodynamics of tolcapone, a novel inhibitor of catechol-O-methyltransferase (COMT), after oral and intravenous administration. Tolcapone 74-83 catechol-O-methyltransferase Homo sapiens 136-140 9754991-6 1998 The volume of distribution was approximately 9 1, and the total clearance was approximately 71.h-l, resulting in a mean plasma half-life of 1.8 h. The degree of erythrocyte COMT inhibition was closely related to tolcapone plasma concentration; a rebound in COMT activity was observed after tolcapone withdrawal. Tolcapone 212-221 catechol-O-methyltransferase Homo sapiens 173-177 9754991-6 1998 The volume of distribution was approximately 9 1, and the total clearance was approximately 71.h-l, resulting in a mean plasma half-life of 1.8 h. The degree of erythrocyte COMT inhibition was closely related to tolcapone plasma concentration; a rebound in COMT activity was observed after tolcapone withdrawal. Tolcapone 290-299 catechol-O-methyltransferase Homo sapiens 173-177 9754991-8 1998 DISCUSSION: Because of its relatively low systemic clearance, tolcapone exhibits only a small degree of first-pass metabolism and a relatively good oral bioavailability, which explains the higher plasma concentrations and stronger COMT inhibition observed with tolcapone compared with entacapone, another COMT inhibitor. Tolcapone 62-71 catechol-O-methyltransferase Homo sapiens 231-235 9754991-8 1998 DISCUSSION: Because of its relatively low systemic clearance, tolcapone exhibits only a small degree of first-pass metabolism and a relatively good oral bioavailability, which explains the higher plasma concentrations and stronger COMT inhibition observed with tolcapone compared with entacapone, another COMT inhibitor. Tolcapone 62-71 catechol-O-methyltransferase Homo sapiens 305-309 9754991-8 1998 DISCUSSION: Because of its relatively low systemic clearance, tolcapone exhibits only a small degree of first-pass metabolism and a relatively good oral bioavailability, which explains the higher plasma concentrations and stronger COMT inhibition observed with tolcapone compared with entacapone, another COMT inhibitor. Tolcapone 261-270 catechol-O-methyltransferase Homo sapiens 231-235 9686768-2 1998 Tolcapone is a potent, reversible catechol-O-methyltransferase (COMT) inhibitor with both peripheral and central activity. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 34-62 9686768-2 1998 Tolcapone is a potent, reversible catechol-O-methyltransferase (COMT) inhibitor with both peripheral and central activity. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 64-68 9681662-0 1998 Catechol-O-methyltransferase: variation in enzyme activity and inhibition by entacapone and tolcapone. Tolcapone 92-101 catechol-O-methyltransferase Homo sapiens 0-28 9633684-4 1998 The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity centrally. Tolcapone 71-80 catechol-O-methyltransferase Homo sapiens 27-31 9633684-4 1998 The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity centrally. Tolcapone 71-80 catechol-O-methyltransferase Homo sapiens 89-93 9633684-4 1998 The new nitrocatechol-type COMT inhibitors entacapone, nitecapone, and tolcapone inhibit COMT in the periphery; tolcapone also inhibits COMT activity centrally. Tolcapone 71-80 catechol-O-methyltransferase Homo sapiens 89-93 9681662-1 1998 OBJECTIVE: The aim of this investigation was to study the variation of catechol-O-methyltransferase (COMT) activity in the human liver, duodenal mucosa and renal cortex, and to investigate the inhibition of COMT by entacapone and tolcapone. Tolcapone 230-239 catechol-O-methyltransferase Homo sapiens 101-105 9681662-1 1998 OBJECTIVE: The aim of this investigation was to study the variation of catechol-O-methyltransferase (COMT) activity in the human liver, duodenal mucosa and renal cortex, and to investigate the inhibition of COMT by entacapone and tolcapone. Tolcapone 230-239 catechol-O-methyltransferase Homo sapiens 207-211 9681662-7 1998 CONCLUSION: Entacapone and tolcapone were powerful inhibitors of COMT and their IC50 estimates were 151 and 773 nM (P = 0.008), respectively, in the liver; consistent results were obtained with the other tissues. Tolcapone 27-36 catechol-O-methyltransferase Homo sapiens 65-69 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. Tolcapone 21-30 catechol-O-methyltransferase Homo sapiens 4-8 9591515-0 1998 Tolcapone: COMT inhibition for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 11-15 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. Tolcapone 90-99 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. Tolcapone 90-99 catechol-O-methyltransferase Homo sapiens 73-77 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). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 47-75 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). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 77-81 9591521-2 1998 In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. Tolcapone 121-130 catechol-O-methyltransferase Homo sapiens 82-110 9591522-0 1998 Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients. Tolcapone 45-54 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. Tolcapone 46-55 catechol-O-methyltransferase Homo sapiens 14-42 9591523-1 1998 We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the "wearing-off" phenomenon on levodopa therapy. Tolcapone 58-67 catechol-O-methyltransferase Homo sapiens 19-47 15094867-3 1998 A new class of drugs, COMT inhibitors, such as tolcapone, also have been introduced into clinical practice. Tolcapone 47-56 catechol-O-methyltransferase Homo sapiens 22-26 9859687-0 1998 [Treatment of Parkinson"s disease with COMT inhibitors: tolcapone]. Tolcapone 56-65 catechol-O-methyltransferase Homo sapiens 39-43 9343116-0 1997 Catechol-O-methyltransferase inhibition with tolcapone reduces the "wearing off" phenomenon and levodopa requirements in fluctuating parkinsonian patients. Tolcapone 45-54 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. Tolcapone 46-55 catechol-O-methyltransferase Homo sapiens 14-42 9339691-1 1997 We studied the new catechol-O-methyltransferase inhibitor tolcapone, 100 and 200 mg, three times daily (tid) in a randomized, double-blind, parallel-group trial involving 202 parkinsonian patients who were experiencing the "wearing-off" phenomenon on levodopa therapy. Tolcapone 58-67 catechol-O-methyltransferase Homo sapiens 19-47 9358559-8 1997 The kinetic parameters for COMT inhibitors were in the following order: K(m) nitecapone > > entacapone > tolcapone; Vmax nitecapone > entacapone > tolcapone; Vmax/K(m) tolcapone > nitecapone > entacapone. Tolcapone 114-123 catechol-O-methyltransferase Rattus norvegicus 27-31 9358559-8 1997 The kinetic parameters for COMT inhibitors were in the following order: K(m) nitecapone > > entacapone > tolcapone; Vmax nitecapone > entacapone > tolcapone; Vmax/K(m) tolcapone > nitecapone > entacapone. Tolcapone 162-171 catechol-O-methyltransferase Rattus norvegicus 27-31 9358559-8 1997 The kinetic parameters for COMT inhibitors were in the following order: K(m) nitecapone > > entacapone > tolcapone; Vmax nitecapone > entacapone > tolcapone; Vmax/K(m) tolcapone > nitecapone > entacapone. Tolcapone 162-171 catechol-O-methyltransferase Rattus norvegicus 27-31 9346324-3 1997 The monkeys received 6-[18F]L-DOPA scans, untreated or after pretreatment with either the peripheral catechol-O-methyltransferase inhibitor nitecapone; the peripheral and central catechol-O-methyltransferase inhibitor tolcapone; the monoamine oxidase inhibitors deprenyl or pargyline; a combination of tolcapone and the monoamine oxidase inhibitors. Tolcapone 218-227 catechol-O-methyltransferase Homo sapiens 179-207 9305320-2 1997 In this double-blind, placebo-controlled trial, we investigated the effect of the catechol-O-methyltransferase inhibitor tolcapone 100 or 200 mg three times daily on activities of daily living and motor function in 298 patients with parkinsonism receiving levodopa but without motor fluctuations. Tolcapone 121-130 catechol-O-methyltransferase Homo sapiens 82-110 9365014-6 1997 All three COMT inhibitors reduced the FDOPA methylation rate constant in plasma, with complete suppression obtained in the case of Ro 40-7592. Tolcapone 131-141 catechol-O-methyltransferase Macaca mulatta 10-14 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. Tolcapone 89-98 catechol-O-methyltransferase Homo sapiens 50-78 9578674-1 1998 Tolcapone is a potent, selective, reversible inhibitor of COMT. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 58-62 9460702-3 1998 In the present study, we analyzed levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in brain homogenates from rats which had received a one-week treatment with tolcapone or phenelzine, inhibitors of COMT and MAO, respectively. Tolcapone 180-189 catechol-O-methyltransferase Rattus norvegicus 219-223 9460702-3 1998 In the present study, we analyzed levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in brain homogenates from rats which had received a one-week treatment with tolcapone or phenelzine, inhibitors of COMT and MAO, respectively. Tolcapone 180-189 monoamine oxidase A Rattus norvegicus 228-231 9537825-5 1997 Surprisingly, tolcapone, another catechol-O-methyltransferase inhibitor, which acts both peripherally and centrally, stimulated respiration in L1210 cells at the lowest concentration studied (5 microM). Tolcapone 14-23 catechol-O-methyltransferase Mus musculus 33-61 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). Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 47-75 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). Tolcapone 11-21 catechol-O-methyltransferase Homo sapiens 47-75 9333106-1 1997 OBJECTIVES: The multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, were assessed in healthy elderly volunteers receiving concomitant carbidopa and levodopa. Tolcapone 86-95 catechol-O-methyltransferase Homo sapiens 105-133 9333106-1 1997 OBJECTIVES: The multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, were assessed in healthy elderly volunteers receiving concomitant carbidopa and levodopa. Tolcapone 86-95 catechol-O-methyltransferase Homo sapiens 135-139 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. Tolcapone 29-38 catechol-O-methyltransferase Homo sapiens 23-27 9337447-17 1997 The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone 36-45 catechol-O-methyltransferase Homo sapiens 4-8 9141056-1 1997 The influence of tolcapone, an inhibitor of catechol-O-methyl transferase, was evaluated on the disposition of apomorphine, a dopamine agonist used to treat Parkinson"s disease, to explain a previously observed increase of duration of the effect of apomorphine associated with tolcapone. Tolcapone 17-26 catechol-O-methyltransferase Rattus norvegicus 44-73 9483396-1 1997 In vivo brain functions analysis was conducted to assess the effect of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor on extracellular levels of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of awake, freely moving eats during GBR 12909-induced blockade of DA uptake. Tolcapone 71-80 catechol-O-methyltransferase Rattus norvegicus 90-118 9483396-1 1997 In vivo brain functions analysis was conducted to assess the effect of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor on extracellular levels of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of awake, freely moving eats during GBR 12909-induced blockade of DA uptake. Tolcapone 71-80 catechol-O-methyltransferase Rattus norvegicus 120-124 9347387-5 1997 Some dopamine-active drugs (e.g. the catechol-O-methyltransferase inhibitor tolcapone; D2/D3 agonists administered intermittently) are active in this procedure but have a time-course comparable to that of conventional antidepressants. Tolcapone 76-85 catechol-O-methyltransferase Homo sapiens 37-65 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. Tolcapone 146-155 catechol-O-methyltransferase Homo sapiens 94-122 9262345-0 1997 Studies on the tight-binding nature of tolcapone inhibition of soluble and membrane-bound rat brain catechol-O-methyltransferase. Tolcapone 39-48 catechol-O-methyltransferase Rattus norvegicus 100-128 9262345-4 1997 In this study, we evaluated the kinetics of rat brain COMT, as well as its mechanisms of inhibition by tolcapone. Tolcapone 103-112 catechol-O-methyltransferase Rattus norvegicus 54-58 9262345-11 1997 In conclusion, our results show that tolcapone is a highly potent tight-binding inhibitor of brain soluble and membrane-bound COMT, but because of difficulties in determining the type of inhibition for this type of compound, we cannot confirm previous claims about the competitive type of COMT inhibition produced by tolcapone. Tolcapone 37-46 catechol-O-methyltransferase Rattus norvegicus 126-130 9262345-11 1997 In conclusion, our results show that tolcapone is a highly potent tight-binding inhibitor of brain soluble and membrane-bound COMT, but because of difficulties in determining the type of inhibition for this type of compound, we cannot confirm previous claims about the competitive type of COMT inhibition produced by tolcapone. Tolcapone 37-46 catechol-O-methyltransferase Rattus norvegicus 289-293 9451720-1 1997 The aim of this study was to evaluate the effects of Tolcapone, a reversible, selective inhibitor of catechol-O-methyltransferase, on the cognitive function of eight patients with advanced Parkinson"s disease. Tolcapone 53-62 catechol-O-methyltransferase Homo sapiens 101-129 9252801-0 1997 The effect of COMT inhibition by tolcapone on tolerability and pharmacokinetics of different levodopa/benserazide formulations. Tolcapone 33-42 catechol-O-methyltransferase Homo sapiens 14-18 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). Tolcapone 157-166 catechol-O-methyltransferase Homo sapiens 107-135 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). Tolcapone 157-166 catechol-O-methyltransferase Homo sapiens 137-141 9252801-5 1997 Continuous inhibition of erythrocyte COMT activity by approximately 75% was observed over 13 h with tolcapone; this was unaffected by levodopa/benserazide formulation. Tolcapone 100-109 catechol-O-methyltransferase Homo sapiens 37-41 9175615-2 1997 Each animal was studied twice: with and without pretreatment of the catechol-O-methyltransferase (COMT) inhibitor Ro 40-7592, tolcapone. Tolcapone 114-124 catechol-O-methyltransferase Homo sapiens 68-96 9175615-2 1997 Each animal was studied twice: with and without pretreatment of the catechol-O-methyltransferase (COMT) inhibitor Ro 40-7592, tolcapone. Tolcapone 114-124 catechol-O-methyltransferase Macaca mulatta 98-102 9175615-6 1997 It is concluded that the COMT inhibitor tolcapone exhibits clear peripheral and central activity. Tolcapone 40-49 catechol-O-methyltransferase Macaca mulatta 25-29 9030401-0 1997 Catechol O-methyltransferase inhibitor tolcapone has minor influence on performance in experimental memory models in rats. Tolcapone 39-48 catechol-O-methyltransferase Rattus norvegicus 0-28 9203084-0 1997 Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson"s disease. Tolcapone 11-20 catechol-O-methyltransferase Homo sapiens 24-52 9203084-1 1997 The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson"s disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 28-56 9008498-2 1997 Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the plasma half-life of levodopa. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 22-50 9404535-0 1996 [COMT inhibition with tolcapone]. Tolcapone 22-31 catechol-O-methyltransferase Homo sapiens 1-5 8879148-0 1996 Interspecies scaling of tolcapone, a new inhibitor of catechol-O-methyltransferase (COMT). Tolcapone 24-33 catechol-O-methyltransferase Homo sapiens 54-82 8879148-0 1996 Interspecies scaling of tolcapone, a new inhibitor of catechol-O-methyltransferase (COMT). Tolcapone 24-33 catechol-O-methyltransferase Homo sapiens 84-88 8829199-0 1996 Minor effect of tolcapone, a catechol-O-methyltransferase inhibitor, on extracellular dopamine levels modified by amphetamine or pargyline: a microdialysis study in anaesthetized rats. Tolcapone 16-25 catechol-O-methyltransferase Rattus norvegicus 29-57 8821869-6 1996 The applicability of the method was demonstrated by the characterization of COMT activity-time courses in human erythrocytes after oral administration of the COMT inhibitor tolcapone. Tolcapone 173-182 catechol-O-methyltransferase Homo sapiens 76-80 8821542-10 1996 The sensitivity of liver and renal COMT activity to tolcapone was markedly dependent on the age, 3-days old rats being more sensitive to tolcapone than older animals. Tolcapone 52-61 catechol-O-methyltransferase Rattus norvegicus 35-39 8821542-10 1996 The sensitivity of liver and renal COMT activity to tolcapone was markedly dependent on the age, 3-days old rats being more sensitive to tolcapone than older animals. Tolcapone 137-146 catechol-O-methyltransferase Rattus norvegicus 35-39 8821542-11 1996 The IC50 values (in nM) for inhibition of liver COMT by tolcapone increased gradually with age, from 41 (26, 65) at the age of 3 days up to 720 (640, 800) at the age of 60 days. Tolcapone 56-65 catechol-O-methyltransferase Rattus norvegicus 48-52 8821542-12 1996 As was found in the liver, IC50 values (in nM) for inhibition of kidney COMT by tolcapone also increased with age, from 8 (6, 10) at the age of 3 days up to 177 (131, 240) at the age of 60 days. Tolcapone 80-89 catechol-O-methyltransferase Rattus norvegicus 72-76 8821542-13 1996 In all experimental groups, the IC50 values for inhibition of liver COMT by tolcapone was higher than those for kidney COMT. Tolcapone 76-85 catechol-O-methyltransferase Rattus norvegicus 68-72 8821542-16 1996 Furthermore, kidney COMT is shown to be more sensitive to inhibition by tolcapone than liver COMT, irrespective of the age of the animal. Tolcapone 72-81 catechol-O-methyltransferase Rattus norvegicus 20-24 8821542-0 1996 Ontogenic aspects of liver and kidney catechol-O-methyltransferase sensitivity to tolcapone. Tolcapone 82-91 catechol-O-methyltransferase Rattus norvegicus 38-66 8821542-2 1996 The present work describes the catechol-O-methyltransferase (COMT) activities in the liver and kidney of developing and adult rats (aged 3, 6, 9, 18, 30 and 60 days; n = 5 per group) and evaluates the enzyme sensitivity to inhibition by tolcapone, a reversible COMT inhibitor. Tolcapone 237-246 catechol-O-methyltransferase Rattus norvegicus 31-59 8821542-2 1996 The present work describes the catechol-O-methyltransferase (COMT) activities in the liver and kidney of developing and adult rats (aged 3, 6, 9, 18, 30 and 60 days; n = 5 per group) and evaluates the enzyme sensitivity to inhibition by tolcapone, a reversible COMT inhibitor. Tolcapone 237-246 catechol-O-methyltransferase Rattus norvegicus 61-65 8821869-6 1996 The applicability of the method was demonstrated by the characterization of COMT activity-time courses in human erythrocytes after oral administration of the COMT inhibitor tolcapone. Tolcapone 173-182 catechol-O-methyltransferase Homo sapiens 158-162 8527287-0 1995 Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa. Tolcapone 71-80 catechol-O-methyltransferase Homo sapiens 56-60 8739811-1 1996 OBJECTIVE: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Tolcapone 94-103 catechol-O-methyltransferase Homo sapiens 113-141 8739811-1 1996 OBJECTIVE: The purpose of this study was to assess the multiple-dose clinical pharmacology of tolcapone, a novel catechol-O-methyltransferase (COMT) inhibitor, in elderly subjects. Tolcapone 94-103 catechol-O-methyltransferase Homo sapiens 143-147 8717160-3 1996 MAO and COMT were inhibited by treatment with pargyline (40 mg/kg) and tolcapone (3 mg/kg followed by 1.5 mg/kg given every 30 min), respectively. Tolcapone 71-80 catechol O-methyltransferase Oryctolagus cuniculus 8-12 8527287-2 1995 Single oral doses of the catechol-O-methyltransferase (COMT) inhibitor tolcapone (10-800 mg) or placebo were administered simultaneously with a dose of levodopa/benserazide 100/25 mg to seven sequential groups of six healthy male subjects in a two-way crossover study. Tolcapone 71-80 catechol-O-methyltransferase Homo sapiens 25-53 8527287-2 1995 Single oral doses of the catechol-O-methyltransferase (COMT) inhibitor tolcapone (10-800 mg) or placebo were administered simultaneously with a dose of levodopa/benserazide 100/25 mg to seven sequential groups of six healthy male subjects in a two-way crossover study. Tolcapone 71-80 catechol-O-methyltransferase Homo sapiens 55-59 8527287-8 1995 Tolcapone caused a rapid and reversible inhibition of COMT activity in erythrocytes in parallel with a dose-dependent decrease in the formation of 3-OMD. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 54-58 8527287-15 1995 Plasma concentrations of tolcapone correlated with inhibition of COMT activity in erythrocytes and suppression of 3-OMD levels, but not with changes in levodopa pharmacokinetics. Tolcapone 25-34 catechol-O-methyltransferase Homo sapiens 65-69 7570359-8 1995 The monoamine oxidase inhibitor, pargyline (75 mg/kg), and the catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592 (40 mg/kg), had small or negligible effects in either region. Tolcapone 110-120 catechol-O-methyltransferase Rattus norvegicus 63-91 7566641-0 1995 Effects of the catechol-O-methyltransferase inhibitor tolcapone in Parkinson"s disease: correlations between concentrations of dopaminergic substances in the plasma and cerebrospinal fluid and clinical improvement. Tolcapone 54-63 catechol-O-methyltransferase Homo sapiens 15-43 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. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 13-41 8635184-0 1995 Acute administration of levodopa-benserazide and tolcapone, a COMT inhibitor, Parkinson"s disease. Tolcapone 49-58 catechol-O-methyltransferase Homo sapiens 62-66 7651456-1 1995 A double-blind, placebo-controlled, crossover trial of tolcapone (RO 40-7592), a potent reversible inhibitor of catechol-O-methyltransferase (COMT), was performed in 10 Parkinson"s disease (PD) patients to determine single-dose safety and efficacy. Tolcapone 66-76 catechol-O-methyltransferase Homo sapiens 142-146 7674141-1 1995 The effect of Madopar (benserazide and L-dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. Tolcapone 135-144 catechol-O-methyltransferase Rattus norvegicus 105-133 7662912-0 1995 Tolcapone, an inhibitor of catechol O-methyltransferase, counteracts memory deficits caused by bilateral cholinotoxin lesions of the basal nuclei of Meynert. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 27-55 7662912-1 1995 Repeated administration of tolcapone, an inhibitor of catechol-O-methyltransferase, was able to partially restore the memory deficits caused by bilateral cholinotoxin (AF64A) lesions in the basal magnocellular nuclei of Meynert. Tolcapone 27-36 catechol-O-methyltransferase Homo sapiens 54-82 7768073-0 1995 Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. Tolcapone 101-110 catechol-O-methyltransferase Homo sapiens 62-90 7768073-1 1995 OBJECTIVES: To assess the tolerability, pharmacokinetics and pharmacodynamics of single oral doses of the novel catechol-O-methyltransferase (COMT) inhibitor tolcapone in healthy volunteers. Tolcapone 158-167 catechol-O-methyltransferase Homo sapiens 112-140 7768073-1 1995 OBJECTIVES: To assess the tolerability, pharmacokinetics and pharmacodynamics of single oral doses of the novel catechol-O-methyltransferase (COMT) inhibitor tolcapone in healthy volunteers. Tolcapone 158-167 catechol-O-methyltransferase Homo sapiens 142-146 7768073-11 1995 Tolcapone caused a rapid and reversible inhibition of COMT activity in erythrocytes. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 54-58 7768073-14 1995 CONCLUSIONS: The novel COMT inhibitor tolcapone was well tolerated at oral doses of 5 to 800 mg. Tolcapone concentration-dependently inhibited COMT activity in erythrocytes and exhibited dose-proportional kinetics. Tolcapone 38-47 catechol-O-methyltransferase Homo sapiens 23-27 7768073-14 1995 CONCLUSIONS: The novel COMT inhibitor tolcapone was well tolerated at oral doses of 5 to 800 mg. Tolcapone concentration-dependently inhibited COMT activity in erythrocytes and exhibited dose-proportional kinetics. Tolcapone 38-47 catechol-O-methyltransferase Homo sapiens 143-147 7768073-14 1995 CONCLUSIONS: The novel COMT inhibitor tolcapone was well tolerated at oral doses of 5 to 800 mg. Tolcapone concentration-dependently inhibited COMT activity in erythrocytes and exhibited dose-proportional kinetics. Tolcapone 97-106 catechol-O-methyltransferase Homo sapiens 23-27 7768073-14 1995 CONCLUSIONS: The novel COMT inhibitor tolcapone was well tolerated at oral doses of 5 to 800 mg. Tolcapone concentration-dependently inhibited COMT activity in erythrocytes and exhibited dose-proportional kinetics. Tolcapone 97-106 catechol-O-methyltransferase Homo sapiens 143-147 7957769-0 1994 The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP(+)-lesioned mice. Tolcapone 19-28 catechol-O-methyltransferase Mus musculus 4-8 8785021-2 1995 Ro 40-7592 (1 and 3 mg/kg, s.c.), a novel COMT inhibitor, 60 min before L-Dopa reinstated both locomotion and rearing during a 2-hr interval after L-Dopa in MPTP mice; control mice were unaffected. Tolcapone 0-10 catechol-O-methyltransferase Mus musculus 42-46 8665546-2 1995 Tolcapone, a reversible COMT inhibitor, was administered in four single ascending doses (50-800 mg) randomly paired with placebo. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 24-28 7737328-0 1995 Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal metabolism of L-dopa and dopamine in rats. Tolcapone 11-20 catechol-O-methyltransferase Rattus norvegicus 30-58 7737328-1 1995 In vivo brain microdialysis was used to assess the effects of tolcapone, a novel central and peripheral inhibitor of catechol-O-methyltransferase on striatal 3,4-dihydroxyphenyl-L-alanine (L-dopa) and dopamine metabolism. Tolcapone 62-71 catechol-O-methyltransferase Rattus norvegicus 117-145 7957769-2 1994 Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o. Tolcapone 81-90 catechol-O-methyltransferase Mus musculus 64-68 7957769-7 1994 In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD. Tolcapone 40-49 catechol-O-methyltransferase Mus musculus 95-99 7996385-5 1994 Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. Tolcapone 0-9 catechol-O-methyltransferase Rattus norvegicus 29-33 7996385-7 1994 It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low Ki). Tolcapone 36-45 catechol-O-methyltransferase Rattus norvegicus 182-186 7996385-7 1994 It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low Ki). Tolcapone 140-149 catechol-O-methyltransferase Rattus norvegicus 182-186 7996385-7 1994 It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low Ki). Tolcapone 36-45 catechol-O-methyltransferase Rattus norvegicus 77-81 11224284-9 1994 These results suggest that selective, reversible COMT inhibitors such as tolcapone may offer an innovative approach to the treatment of depression, in addition to their potential therapeutic use in Parkinson"s disease. Tolcapone 73-82 catechol-O-methyltransferase Rattus norvegicus 49-53 7835624-4 1994 Entacapone, nitecapone and tolcapone are nitrocatechol-type potent COMT inhibitors in vitro (Ki in nanomolar range). Tolcapone 27-36 catechol-O-methyltransferase Homo sapiens 67-71 7835624-12 1994 In man, entacapone, nitecapone and tolcapone all inhibit dose dependently the COMT activity in erythrocytes. Tolcapone 35-44 catechol-O-methyltransferase Homo sapiens 78-82 1613509-0 1992 Extracellular concentrations of dopamine and metabolites in the rat caudate after oral administration of a novel catechol-O-methyltransferase inhibitor Ro 40-7592. Tolcapone 152-162 catechol-O-methyltransferase Rattus norvegicus 113-141 27520516-5 1994 In human volunteers, entacapone, nitecapone and tolcapone inhibit dose-dependently COMT activity of erythrocytes. Tolcapone 48-57 catechol-O-methyltransferase Homo sapiens 83-87 8216760-6 1993 Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS. Tolcapone 18-28 catechol-O-methyltransferase Rattus norvegicus 32-60 1381981-1 1992 In vivo microdialysis was used to examine the effect of two new catechol-O-methyltransferase (COMT) inhibitors, Ro 40-7592 and OR-611, on extracellular levels of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in rat striatum. Tolcapone 112-122 catechol-O-methyltransferase Rattus norvegicus 94-98 8255478-0 1993 Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Tolcapone 39-48 catechol-O-methyltransferase Homo sapiens 0-28 8255478-4 1993 We administered levodopa/carbidopa in combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone 76-85 catechol-O-methyltransferase Homo sapiens 116-144 8255478-4 1993 We administered levodopa/carbidopa in combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of catechol-O-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone 87-97 catechol-O-methyltransferase Homo sapiens 116-144 8099689-0 1993 Ro 40-7592, a COMT inhibitor, plus levodopa in Parkinson"s disease. Tolcapone 0-10 catechol-O-methyltransferase Homo sapiens 14-18 1383428-2 1992 Inhibitors of monoamine oxidase (MAO; pargyline) and catechol-O-methyltransferase (COMT; Ro 40-7592) were administered, either separately or in conjunction, at doses sufficient to block these enzymes in the CNS. Tolcapone 89-99 catechol-O-methyltransferase Rattus norvegicus 83-87 1613509-1 1992 The effect of the systemic administration of a novel, orally active, catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592, on the in vivo extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was studied by transcerebral microdialysis in the dorsal caudate of freely moving rats. Tolcapone 116-126 catechol-O-methyltransferase Rattus norvegicus 69-97 1613509-1 1992 The effect of the systemic administration of a novel, orally active, catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592, on the in vivo extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was studied by transcerebral microdialysis in the dorsal caudate of freely moving rats. Tolcapone 116-126 catechol-O-methyltransferase Rattus norvegicus 99-103 1549240-1 1992 We administered Ro 40-7592, an inhibitor of the enzyme catechol-O-methyltransferase (COMT) that crosses the blood-brain barrier, to rats and monitored extracellular catecholamine levels in the corpus striatum before and after the intraperitoneal administration of a bolus of l-dopa. Tolcapone 16-26 catechol-O-methyltransferase Rattus norvegicus 55-83 1628144-14 1992 Ro 40-7592 was a broad spectrum COMT inhibitor decreasing striatal and hypothalamic 3-OMD (always to less than 30%), HVA (to less than 50%) and 3-MT levels (to less than 23%) significantly both at 1 and 3 h. It was more potent than OR-611. Tolcapone 0-10 catechol-O-methyltransferase Rattus norvegicus 32-36 1549240-1 1992 We administered Ro 40-7592, an inhibitor of the enzyme catechol-O-methyltransferase (COMT) that crosses the blood-brain barrier, to rats and monitored extracellular catecholamine levels in the corpus striatum before and after the intraperitoneal administration of a bolus of l-dopa. Tolcapone 16-26 catechol-O-methyltransferase Rattus norvegicus 85-89 1867835-2 1991 Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Tolcapone 131-141 catechol-O-methyltransferase Macaca mulatta 90-118 1536715-5 1992 After pretreatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 +/- 0.0015 min-1) for (beta-11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(beta-11C)-L-dopa (0.0092 +/- 0.0015 min-1). Tolcapone 129-139 catechol-O-methyltransferase Macaca mulatta 77-111 1536715-5 1992 After pretreatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 +/- 0.0015 min-1) for (beta-11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(beta-11C)-L-dopa (0.0092 +/- 0.0015 min-1). Tolcapone 129-139 catechol-O-methyltransferase Macaca mulatta 113-117 1639913-0 1992 Determination of the catechol-O-methyltransferase inhibitor Ro 40-7592 in human plasma by high-performance liquid chromatography with coulometric detection. Tolcapone 60-70 catechol-O-methyltransferase Homo sapiens 21-49 1639913-1 1992 A sensitive and specific high-performance liquid chromatographic method has been developed to measure the catechol-O-methyl-transferase (COMT) inhibitor 3,4-dihydroxy-4"-methyl-5-nitrobenzophenone (Ro 40-7592) in human plasma. Tolcapone 153-196 catechol-O-methyltransferase Homo sapiens 106-135 1639913-1 1992 A sensitive and specific high-performance liquid chromatographic method has been developed to measure the catechol-O-methyl-transferase (COMT) inhibitor 3,4-dihydroxy-4"-methyl-5-nitrobenzophenone (Ro 40-7592) in human plasma. Tolcapone 153-196 catechol-O-methyltransferase Homo sapiens 137-141 1639913-1 1992 A sensitive and specific high-performance liquid chromatographic method has been developed to measure the catechol-O-methyl-transferase (COMT) inhibitor 3,4-dihydroxy-4"-methyl-5-nitrobenzophenone (Ro 40-7592) in human plasma. Tolcapone 198-208 catechol-O-methyltransferase Homo sapiens 106-135 1639913-1 1992 A sensitive and specific high-performance liquid chromatographic method has been developed to measure the catechol-O-methyl-transferase (COMT) inhibitor 3,4-dihydroxy-4"-methyl-5-nitrobenzophenone (Ro 40-7592) in human plasma. Tolcapone 198-208 catechol-O-methyltransferase Homo sapiens 137-141 1847521-9 1991 The COMT activity of recombinant protein was inhibited competitively (IC50 = 700 nM) by the selective COMT inhibitor Ro 40-7592. Tolcapone 117-127 catechol-O-methyltransferase Homo sapiens 4-8 1847521-9 1991 The COMT activity of recombinant protein was inhibited competitively (IC50 = 700 nM) by the selective COMT inhibitor Ro 40-7592. Tolcapone 117-127 catechol-O-methyltransferase Homo sapiens 102-106 1867835-2 1991 Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Tolcapone 131-141 catechol-O-methyltransferase Macaca mulatta 120-124 2239490-0 1990 Ro 40-7592, a novel, very potent, and orally active inhibitor of catechol-O-methyltransferase: a pharmacological study in rats. Tolcapone 0-10 catechol-O-methyltransferase Rattus norvegicus 65-93 1977408-0 1990 Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson"s disease. Tolcapone 41-51 catechol-O-methyltransferase Rattus norvegicus 59-63 2089102-0 1990 Ro 40-7592: inhibition of COMT in rat brain and extracerebral tissues. Tolcapone 0-10 catechol-O-methyltransferase Rattus norvegicus 26-30 2089102-2 1990 Ro 40-7592 was found to inhibit COMT in a competitive fashion both in the CNS and in the periphery (Ki for the liver enzyme = 30 nM). Tolcapone 0-10 catechol-O-methyltransferase Rattus norvegicus 32-36 1977408-1 1990 Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4"-methyl-5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Tolcapone 46-56 catechol-O-methyltransferase Rattus norvegicus 110-114 34225162-4 2021 It has been reported that 1-tetralone and 1-indanone derivatives are potent and specific inhibitors of MAO-B, while compounds containing the nitrocatechol moiety (e.g. tolcapone and entacapone) are often potent COMT inhibitors. Tolcapone 168-177 catechol-O-methyltransferase Homo sapiens 211-215 34390874-5 2021 Using arterial spin labeling (ASL) and a double-blind, within-subject design, perfusion was measured in 75 healthy, genotyped participants once each after administration of tolcapone (a COMT inhibitor), bromocriptine (a DA D2/3 agonist), and placebo. Tolcapone 173-182 catechol-O-methyltransferase Homo sapiens 186-190 34652342-5 2021 Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Tolcapone 44-47 nitric oxide synthase 2, inducible Mus musculus 209-213 34652342-5 2021 Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Tolcapone 44-47 tumor necrosis factor Mus musculus 215-218 34652342-5 2021 Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Tolcapone 44-47 interleukin 6 Mus musculus 224-227 34652342-5 2021 Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Tolcapone 265-268 nitric oxide synthase 2, inducible Mus musculus 209-213 34652342-5 2021 Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Tolcapone 265-268 tumor necrosis factor Mus musculus 215-218 34652342-5 2021 Mice were fed sugar water (SUG; control) or TCW for a week and then subjected to 60 min of liver ischemia followed by reperfusion for 6 h. Plasma alanine transaminase levels, tissue damage, and mRNA levels of Nos2, Tnf, and Il6 were significantly lower in mice fed TCW prior to I/R. Tolcapone 265-268 interleukin 6 Mus musculus 224-227 34652342-10 2021 The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Tolcapone 143-146 nitric oxide synthase 2, inducible Mus musculus 14-18 34652342-10 2021 The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Tolcapone 143-146 interleukin 1 beta Mus musculus 20-24 34652342-10 2021 The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Tolcapone 143-146 tumor necrosis factor Mus musculus 26-29 34652342-10 2021 The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Tolcapone 143-146 interleukin 6 Mus musculus 35-38 34652342-10 2021 The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Tolcapone 143-146 interleukin 10 Mus musculus 60-64 34652342-10 2021 The levels of Nos2, Il1b, Tnf, and Il6 were decreased while Il10 and Hmox1 mRNA levels were significantly up-regulated upon LPS stimulation of TCW pretreated RAW264.7 macrophages. Tolcapone 143-146 heme oxygenase 1 Mus musculus 69-74 34310432-2 2021 Tolcapone is a catechol-O-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 15-44 34310432-2 2021 Tolcapone is a catechol-O-methyl-transferase (COMT) enzyme inhibitor that augments cortical dopaminergic transmission. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 46-50 34252268-10 2021 Per residue decomposition analysis revealed similar crucial residues involved in the favorable binding of c38 and tolcapone implicated its increased inhibitory capacity on COMT in preventing PD. Tolcapone 114-123 catechol-O-methyltransferase Homo sapiens 172-176 35443830-5 2022 Volunteers were administered either a single 200 mg dose of the brain-penetrant COMT inhibitor tolcapone or placebo in a double-blind, randomised manner. Tolcapone 95-104 catechol-O-methyltransferase Homo sapiens 80-84 34253715-5 2021 Each subject received both placebo and the catechol-O-methyl transferase inhibitor tolcapone, which increases cortical dopamine tone, in randomized, double-blind, counterbalanced fashion. Tolcapone 83-92 catechol-O-methyltransferase Homo sapiens 43-72 35523943-0 2022 Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone. Tolcapone 134-143 catechol-O-methyltransferase Homo sapiens 53-57 35631665-6 2022 Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Tolcapone 41-43 RAN pseudogene 1 Homo sapiens 15-18 35631665-6 2022 Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Tolcapone 158-160 RAN pseudogene 1 Homo sapiens 15-18 35523943-4 2022 This study was a randomized, placebo-controlled, pharmacogenetic trial of the COMT inhibitor tolcapone. Tolcapone 93-102 catechol-O-methyltransferase Homo sapiens 78-82 35523943-10 2022 Tolcapone, relative to placebo, reduced COMT activity in all genotype groups. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 40-44 35523943-11 2022 COMT genotype moderated tolcapone"s effect on drinking during the medication period and in the bar lab, such that tolcapone, relative to placebo, reduced drinking only among val-allele homozygotes. Tolcapone 24-33 catechol-O-methyltransferase Homo sapiens 0-4 35523943-11 2022 COMT genotype moderated tolcapone"s effect on drinking during the medication period and in the bar lab, such that tolcapone, relative to placebo, reduced drinking only among val-allele homozygotes. Tolcapone 114-123 catechol-O-methyltransferase Homo sapiens 0-4 33789133-5 2021 Here, 76 healthy males, homozygous for the functional COMT Val158Met polymorphism, were administered either the COMT inhibitor tolcapone or placebo in a double-blind, randomised design. Tolcapone 127-136 catechol-O-methyltransferase Homo sapiens 112-116 35352593-1 2022 PURPOSE: To investigate the effect of tolcapone on cerebrospinal fluid (CSF) transthyretin (TTR) tetramer stability in patients with hereditary transthyretin (ATTRv) amyloidosis. Tolcapone 38-47 transthyretin Homo sapiens 77-90 35352593-1 2022 PURPOSE: To investigate the effect of tolcapone on cerebrospinal fluid (CSF) transthyretin (TTR) tetramer stability in patients with hereditary transthyretin (ATTRv) amyloidosis. Tolcapone 38-47 transthyretin Homo sapiens 92-95 35352593-1 2022 PURPOSE: To investigate the effect of tolcapone on cerebrospinal fluid (CSF) transthyretin (TTR) tetramer stability in patients with hereditary transthyretin (ATTRv) amyloidosis. Tolcapone 38-47 transthyretin Homo sapiens 144-157 35352593-9 2022 Orally administered tolcapone significantly increased CSF TTR concentration and decreased monomer content under semi-denaturing conditions. Tolcapone 20-29 transthyretin Homo sapiens 58-61 35044481-3 2022 The available COMT inhibitors, entacapone, opicapone and tolcapone, differ pharmacokinetically in terms of their half-lives with implications for the dose frequency, in their indication requirements and in their spectrum of side effects, including diarrhea and yellow discoloration of urine. Tolcapone 57-66 catechol-O-methyltransferase Homo sapiens 14-18 33415500-1 2021 PURPOSE: Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson"s disease (PD). Tolcapone 9-18 catechol-O-methyltransferase Homo sapiens 37-65 33289420-0 2021 Tissue and interspecies comparison of catechol-O-methyltransferase mediated catalysis of 6-O-methylation of esculetin to scopoletin and its inhibition by entacapone and tolcapone. Tolcapone 169-178 catechol-O-methyltransferase Rattus norvegicus 38-66 33925044-2 2021 Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. Tolcapone 83-86 apolipoprotein B mRNA editing enzyme catalytic subunit 3B Homo sapiens 46-54 33289420-3 2021 Furthermore, we compared the inhibition potencies and mechanisms of two clinically used COMT inhibitors, entacapone and tolcapone, in these species. Tolcapone 120-129 catechol-O-methyltransferase Rattus norvegicus 88-92 33289420-9 2021 Both entacapone and tolcapone are potent COMT inhibitors, but their inhibition mechanisms differ. Tolcapone 20-29 catechol-O-methyltransferase Rattus norvegicus 41-45 32324953-5 2021 Recently, we have repurposed tolcapone as a molecule to treat systemic ATTR. Tolcapone 29-38 transthyretin Homo sapiens 71-75 32324953-6 2021 Crystal structures and biophysical analysis converge to demonstrate that tolcapone binds with high affinity and specificity to three unstable leptomeningeal TTR variants, stabilizing them and, consequently inhibiting their aggregation. Tolcapone 73-82 transthyretin Homo sapiens 157-160 33038358-0 2020 Improved functional and histochemical outcomes in l-DOPA plus tolcapone treated VMAT2-deficient mice. Tolcapone 62-71 solute carrier family 18 (vesicular monoamine), member 2 Mus musculus 80-85 33038358-11 2020 Overall, we observed a moderate functional and histopathological improvement effect by chronic dopamine replacement when combined with tolcapone in vesicular monoamine transporter 2-deficient mice. Tolcapone 135-144 solute carrier family 18 (vesicular monoamine), member 2 Mus musculus 148-181 33054556-5 2021 To test this hypothesis, tolcapone, a catechol-O-methyltransferase inhibitor that preferentially increases cortical dopamine tone, was administered in a randomized, double-blind, placebo-controlled, within-subject fashion to 49 participants who completed a hierarchical working memory task that varied maintenance and gating demands. Tolcapone 25-34 catechol-O-methyltransferase Homo sapiens 38-66 32617646-0 2020 The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder. Tolcapone 43-52 catechol-O-methyltransferase Homo sapiens 4-32 32791384-0 2020 Interactions of tolcapone analogues as stabilizers of the amyloidogenic protein transthyretin. Tolcapone 16-25 transthyretin Homo sapiens 80-93 32791384-2 2020 TTR stabilizers, such as tolcapone, an FDA approved drug for Parkinson"s disease, are able to interact with residues of the thyroxine-binding sites of TTR, both wild type and pathogenic mutant forms, thereby stabilizing its tetrameric native state and inhibiting amyloidogenesis. Tolcapone 25-34 transthyretin Homo sapiens 0-3 32791384-2 2020 TTR stabilizers, such as tolcapone, an FDA approved drug for Parkinson"s disease, are able to interact with residues of the thyroxine-binding sites of TTR, both wild type and pathogenic mutant forms, thereby stabilizing its tetrameric native state and inhibiting amyloidogenesis. Tolcapone 25-34 transthyretin Homo sapiens 151-154 32791384-5 2020 In the two TTR-ligand complexes the tolcapone analogues establish mainly H-bond and hydrophobic interactions with residues of the thyroxine-binding site of the TTR tetramer. Tolcapone 36-45 transthyretin Homo sapiens 11-14 32791384-5 2020 In the two TTR-ligand complexes the tolcapone analogues establish mainly H-bond and hydrophobic interactions with residues of the thyroxine-binding site of the TTR tetramer. Tolcapone 36-45 transthyretin Homo sapiens 160-163 32791384-8 2020 Our data, coupled with previously reported data on the pharmacokinetics properties in humans of tolcapone and 3-O-methyltolcapone, further support the relevance of the latter tolcapone analogue as TTR stabilizer. Tolcapone 120-129 transthyretin Homo sapiens 197-200 32617646-3 2020 OBJECTIVES: To determine if the catechol-O-methyltransferase (COMT) inhibitor tolcapone can attenuate alcohol consumption in individuals with AUD and whether this attenuation correlates with tolcapone-induced changes in laboratory-based decision-making tasks. Tolcapone 78-87 catechol-O-methyltransferase Homo sapiens 62-66 32617646-9 2020 CONCLUSIONS: These data demonstrate that COMT inhibitors such as tolcapone may be useful therapeutics for AUD. Tolcapone 65-74 catechol-O-methyltransferase Homo sapiens 41-45 32583097-10 2020 In addition, we have identified novel FXR antagonistic effects of well-studied hepatotoxic drugs, including bosentan, tolcapone and ritonavir. Tolcapone 118-127 nuclear receptor subfamily 1 group H member 4 Homo sapiens 38-41 32474681-7 2020 We benchmarked the performance of the novel COMT inhibitors to the effects produced by the known COMT inhibitor tolcapone. Tolcapone 112-121 catechol-O-methyltransferase Rattus norvegicus 44-48 32474681-7 2020 We benchmarked the performance of the novel COMT inhibitors to the effects produced by the known COMT inhibitor tolcapone. Tolcapone 112-121 catechol-O-methyltransferase Rattus norvegicus 97-101 32584021-6 2020 More importantly, tolcapone significantly improved the spatial cognition and recognition of Abeta-treated mice. Tolcapone 18-27 amyloid beta (A4) precursor protein Mus musculus 92-97 32687872-2 2020 However, the relationship between tolcapone administration with fatal cases of drug-induced liver damage gave COMT inhibitors a bad reputation as hepatotoxic drugs. Tolcapone 34-43 catechol-O-methyltransferase Homo sapiens 110-114 32687872-3 2020 Thus, there is a pressing need to feed the pipeline with safe COMT inhibitors to replace tolcapone, the only currently available COMT inhibitor that effectively reaches the brain. Tolcapone 89-98 catechol-O-methyltransferase Homo sapiens 129-133 32444540-2 2020 OBJECTIVE: To determine the effect of tolcapone, a specific inhibitor of Catechol-O-Methyltransferase (COMT), in patients with bvFTD. Tolcapone 38-47 catechol-O-methyltransferase Homo sapiens 73-101 32341121-4 2020 We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n=14) in a randomized double-blind placebo-controlled crossover study. Tolcapone 134-143 catechol-O-methyltransferase Homo sapiens 88-116 32341121-4 2020 We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers (n=14) in a randomized double-blind placebo-controlled crossover study. Tolcapone 134-143 catechol-O-methyltransferase Homo sapiens 118-122 32341121-12 2020 Here we examined whether increasing frontal dopamine tone via the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in a group of gamblers. Tolcapone 112-121 catechol-O-methyltransferase Homo sapiens 66-94 32341121-12 2020 Here we examined whether increasing frontal dopamine tone via the catechol-O-methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in a group of gamblers. Tolcapone 112-121 catechol-O-methyltransferase Homo sapiens 96-100 32708961-2 2020 Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 45-74 32708961-3 2020 In recent years, it has been shown that tolcapone is a potent inhibitor of the amyloid aggregation process of the transthyretin protein, and acts by stabilizing the structure of the protein, reducing the progression of familial amyloid polyneuropathy. Tolcapone 40-49 transthyretin Homo sapiens 114-127 32444540-2 2020 OBJECTIVE: To determine the effect of tolcapone, a specific inhibitor of Catechol-O-Methyltransferase (COMT), in patients with bvFTD. Tolcapone 38-47 catechol-O-methyltransferase Homo sapiens 103-107 31187152-4 2019 Sub-study II: COMT rs4680 homozygous subjects (Val/Val and Met/Met) from sub-study I received the COMT enzyme inhibitor tolcapone (200 mg) followed by IV THC or placebo on two additional test days. Tolcapone 120-129 catechol-O-methyltransferase Homo sapiens 14-18 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 0-3 nitric oxide synthase 2 Rattus norvegicus 14-18 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 0-3 AKT serine/threonine kinase 1 Rattus norvegicus 52-55 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 0-3 mitogen-activated protein kinase 8 Rattus norvegicus 60-63 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 0-3 nitric oxide synthase 2 Rattus norvegicus 140-144 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 124-127 nitric oxide synthase 2 Rattus norvegicus 14-18 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 124-127 AKT serine/threonine kinase 1 Rattus norvegicus 52-55 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 124-127 mitogen-activated protein kinase 8 Rattus norvegicus 102-105 32863888-6 2020 TCW inhibited iNOS expression through activation of AKT and JNK pathways since inhibition of PI3K and JNK signaling reduced TCW"s effect on iNOS protein expression and activity. Tolcapone 124-127 nitric oxide synthase 2 Rattus norvegicus 140-144 31231499-0 2019 Catechol-o-methyltransferase inhibitor tolcapone improves learning and memory in naive but not in haloperidol challenged rats. Tolcapone 39-48 catechol-O-methyltransferase Rattus norvegicus 0-28 31491076-4 2019 Incubation of PC12 cells with tolcapone, a highly potent and selective COMT inhibitor, increased the concentrations of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) while reducing the metabolites 3-methoxytyramine (3-MT) and homovanillic acid (HVA) in the cell culture medium. Tolcapone 30-39 catechol-O-methyltransferase Rattus norvegicus 71-75 31119947-0 2019 Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Tolcapone 83-92 transthyretin Homo sapiens 0-13 31119947-0 2019 Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Tolcapone 83-92 catechol-O-methyltransferase Homo sapiens 44-72 31119947-0 2019 Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Tolcapone 83-92 transthyretin Homo sapiens 117-121 31119947-0 2019 Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Tolcapone 94-101 transthyretin Homo sapiens 0-13 31119947-0 2019 Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Tolcapone 94-101 catechol-O-methyltransferase Homo sapiens 44-72 31119947-0 2019 Transthyretin stabilization activity of the catechol-O-methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: proof-of-concept study. Tolcapone 94-101 transthyretin Homo sapiens 117-121 31119947-1 2019 Objective: To assess the transthyretin (TTR) stabilization activity of tolcapone (SOM0226) in patients with hereditary ATTR amyloidosis, asymptomatic carriers and healthy volunteers. Tolcapone 71-80 transthyretin Homo sapiens 25-38 31119947-1 2019 Objective: To assess the transthyretin (TTR) stabilization activity of tolcapone (SOM0226) in patients with hereditary ATTR amyloidosis, asymptomatic carriers and healthy volunteers. Tolcapone 71-80 transthyretin Homo sapiens 40-43 31119947-1 2019 Objective: To assess the transthyretin (TTR) stabilization activity of tolcapone (SOM0226) in patients with hereditary ATTR amyloidosis, asymptomatic carriers and healthy volunteers. Tolcapone 71-80 transthyretin Homo sapiens 119-123 31119947-10 2019 Conclusions: The ability of tolcapone for stabilizing TTR supports further development and repositioning of the drug for the treatment of ATTR amyloidosis. Tolcapone 28-37 transthyretin Homo sapiens 54-57 31119947-10 2019 Conclusions: The ability of tolcapone for stabilizing TTR supports further development and repositioning of the drug for the treatment of ATTR amyloidosis. Tolcapone 28-37 transthyretin Homo sapiens 138-142 31231499-3 2019 Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naive and haloperidol-challenged rats. Tolcapone 51-60 catechol-O-methyltransferase Rattus norvegicus 36-40 31231499-3 2019 Our aim was to assess the effect of COMT inhibitor tolcapone (TCP) on learning and memory in naive and haloperidol-challenged rats. Tolcapone 62-65 catechol-O-methyltransferase Rattus norvegicus 36-40 30406194-5 2018 On test days, the catechol-o-methyl-transferase (COMT) inhibitor tolcapone was administered prior to conditioning. Tolcapone 65-74 catechol-O-methyltransferase Rattus norvegicus 18-47 30367738-0 2019 Metabolism and elimination of the catechol-o-methyltransferase inhibitor tolcapone in the horse. Tolcapone 73-82 catechol O-methyltransferase Equus caballus 34-62 30367827-5 2018 We found that clonazepam, flunitrazepam, flutamide, nilutamide, nimesulide, and nimetazepam were substantially reduced by recombinant AOX1 and HLC, whereas azelnidipine, nifedipine, and nimodipine were slightly reduced and metronidazole and tolcapone were not reduced. Tolcapone 241-250 aldehyde oxidase 1 Homo sapiens 134-138 30406194-5 2018 On test days, the catechol-o-methyl-transferase (COMT) inhibitor tolcapone was administered prior to conditioning. Tolcapone 65-74 catechol-O-methyltransferase Rattus norvegicus 49-53 29020372-6 2017 Tolcapone reduced false alarm rate (d=0.8) and enhanced frontal P200 amplitude during correctly identified nontarget trials (d=0.6) in low-baseline 5 Choice-Continuous Performance Test performers and had opposite effects in high performers (d=0.5 and d=0.25, respectively). Tolcapone 0-9 AT-rich interaction domain 2 Homo sapiens 64-68 30295310-10 2018 TCW treatment reversed the HS-induced proinflammatory state through activation of the Nrf2-assisted antioxidant response, which restored the testicular damage. Tolcapone 0-3 nuclear factor, erythroid derived 2, like 2 Mus musculus 86-90 30027496-3 2018 OBJECTIVES: Here we hypothesize that the catechol-O-methyltransferase (COMT) inhibitor tolcapone, which increases dopamine tone in frontal cortex (Ceravolo et al Synapse 43:201-207, 2002), improves time perception, with predictive behavioral, genetic, and neurobiological components. Tolcapone 87-96 catechol-O-methyltransferase Homo sapiens 41-69 30027496-3 2018 OBJECTIVES: Here we hypothesize that the catechol-O-methyltransferase (COMT) inhibitor tolcapone, which increases dopamine tone in frontal cortex (Ceravolo et al Synapse 43:201-207, 2002), improves time perception, with predictive behavioral, genetic, and neurobiological components. Tolcapone 87-96 catechol-O-methyltransferase Homo sapiens 71-75 29472644-1 2018 Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase (COMT) devoid of psychostimulant properties, improves cognition and cortical information processing in rested volunteers, depending on the genotype of the functional Val158Met polymorphism of COMT. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 52-80 29472644-1 2018 Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase (COMT) devoid of psychostimulant properties, improves cognition and cortical information processing in rested volunteers, depending on the genotype of the functional Val158Met polymorphism of COMT. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 82-86 29472644-1 2018 Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase (COMT) devoid of psychostimulant properties, improves cognition and cortical information processing in rested volunteers, depending on the genotype of the functional Val158Met polymorphism of COMT. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 273-277 29472644-5 2018 Subsequently, we tested in an independent group of 30 young men whether selective inhibition of COMT activity with tolcapone counteracts attentional and neurophysiological markers of elevated sleep need in a genotype-dependent manner. Tolcapone 115-124 catechol-O-methyltransferase Homo sapiens 96-100 29427081-2 2018 We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility. Tolcapone 67-76 catechol-O-methyltransferase Homo sapiens 80-108 29427081-2 2018 We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility. Tolcapone 67-76 catechol-O-methyltransferase Homo sapiens 110-114 29310047-2 2018 In the current experiments, the COMT inhibitor tolcapone was utilized in an operant behavioral model of reinforcer-seeking and drinking to determine if this compound was capable of remediating the excessive seeking and drinking phenotype of the alcohol-preferring P rat. Tolcapone 47-56 catechol-O-methyltransferase Rattus norvegicus 32-36 29310047-11 2018 These data complement our previous findings in which tolcapone reduced cue-evoked responses in P rats and further suggest clinical utility of COMT inhibitors in the treatment of addiction disorders, specifically in male high drinkers. Tolcapone 53-62 catechol-O-methyltransferase Rattus norvegicus 142-146 29697034-7 2018 The chalcone class of compounds is well known to potently inhibit MAO-B, while nitrocatechol derivatives (e.g. tolcapone and entacapone) are clinically used COMT inhibitors. Tolcapone 111-120 catechol-O-methyltransferase Homo sapiens 157-161 29375679-9 2018 Tolcapone, a catechol-O-methyl transferase (COMT) inhibitor, can improve the motor function of patients with PD, especially exercise and muscle stiffness. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 13-42 29375679-9 2018 Tolcapone, a catechol-O-methyl transferase (COMT) inhibitor, can improve the motor function of patients with PD, especially exercise and muscle stiffness. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 44-48 28916530-5 2017 The results suggest that BIA 9-1079, nebicapone, and tolcapone inhibit BCRP in a concentration-dependent manner. Tolcapone 53-62 ATP binding cassette subfamily G member 2 Canis lupus familiaris 71-75 29688484-0 2018 Effect of the Catechol-O-Methyltransferase Inhibitors Tolcapone and Entacapone on Fatty Acid Metabolism in HepaRG Cells. Tolcapone 54-63 catechol-O-methyltransferase Homo sapiens 14-42 29688484-1 2018 Tolcapone and entacapone are catechol-O-methyltransferase inhibitors used in patients with Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 29-57 29688484-8 2018 Tolcapone-reduced mRNA and protein expression of long-chain acyl-CoA synthetase 1 (ACSL1) and protein expression of ACSL5, whereas entacapone did not affect ACSL expression. Tolcapone 0-9 acyl-CoA synthetase long chain family member 1 Homo sapiens 49-81 29688484-8 2018 Tolcapone-reduced mRNA and protein expression of long-chain acyl-CoA synthetase 1 (ACSL1) and protein expression of ACSL5, whereas entacapone did not affect ACSL expression. Tolcapone 0-9 acyl-CoA synthetase long chain family member 1 Homo sapiens 83-88 29688484-8 2018 Tolcapone-reduced mRNA and protein expression of long-chain acyl-CoA synthetase 1 (ACSL1) and protein expression of ACSL5, whereas entacapone did not affect ACSL expression. Tolcapone 0-9 acyl-CoA synthetase long chain family member 5 Homo sapiens 116-121 29688484-9 2018 Tolcapone increased mRNA expression of the fatty acid transporter CD36/FAT, impaired the secretion of ApoB100 by HepaRG cells and reduced the mRNA expression of ApoB100, but did not relevantly affect markers of fatty acid binding, lipid droplet formation and microsomal lipid transfer. Tolcapone 0-9 apolipoprotein B Homo sapiens 102-109 29688484-9 2018 Tolcapone increased mRNA expression of the fatty acid transporter CD36/FAT, impaired the secretion of ApoB100 by HepaRG cells and reduced the mRNA expression of ApoB100, but did not relevantly affect markers of fatty acid binding, lipid droplet formation and microsomal lipid transfer. Tolcapone 0-9 apolipoprotein B Homo sapiens 161-168 29684908-1 2018 In this work, voltammetric data recorded by a glassy carbon electrode (GCE) was used to investigate the interactions of tolcapone (Tasmar, TAS) with human serum albumin (HSA) at the electrode surface. Tolcapone 120-129 THAS Homo sapiens 139-142 29684908-1 2018 In this work, voltammetric data recorded by a glassy carbon electrode (GCE) was used to investigate the interactions of tolcapone (Tasmar, TAS) with human serum albumin (HSA) at the electrode surface. Tolcapone 120-129 albumin Homo sapiens 155-168 29684908-1 2018 In this work, voltammetric data recorded by a glassy carbon electrode (GCE) was used to investigate the interactions of tolcapone (Tasmar, TAS) with human serum albumin (HSA) at the electrode surface. Tolcapone 120-129 albumin Homo sapiens 170-173 29087505-5 2018 PD1-/- mice treated with anti-CTLA-4 and troglitazone or tolcapone displayed liver injury as determined by ALT levels and histology, while pioglitazone and entacapone showed less signs of liver injury. Tolcapone 57-66 programmed cell death 1 Mus musculus 0-3 29087505-5 2018 PD1-/- mice treated with anti-CTLA-4 and troglitazone or tolcapone displayed liver injury as determined by ALT levels and histology, while pioglitazone and entacapone showed less signs of liver injury. Tolcapone 57-66 glutamic pyruvic transaminase, soluble Mus musculus 107-110 29020372-7 2017 Tolcapone"s effect on frontal P200 amplitude and false alarm rate was correlated (rs=-0.4, P=.05). Tolcapone 0-9 AT-rich interaction domain 2 Homo sapiens 30-34 28429453-0 2017 Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma. Tolcapone 0-9 Rho guanine nucleotide exchange factor (GEF) 16 Mus musculus 90-103 28526448-0 2017 The catechol-O-methyltransferase inhibitors tolcapone and entacapone uncouple and inhibit the mitochondrial respiratory chain in HepaRG cells. Tolcapone 44-53 catechol-O-methyltransferase Homo sapiens 4-32 28526448-1 2017 The catechol-O-methyltransferase inhibitor tolcapone causes hepatotoxicity and mitochondrial damage in animal models. Tolcapone 43-52 catechol-O-methyltransferase Homo sapiens 4-32 28429453-2 2017 Tolcapone, a drug commonly used in the treatment of Parkinson"s disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. Tolcapone 0-9 catechol-O-methyltransferase Mus musculus 98-102 28429453-2 2017 Tolcapone, a drug commonly used in the treatment of Parkinson"s disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. Tolcapone 138-147 catechol-O-methyltransferase Mus musculus 98-102 28429453-3 2017 In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Tolcapone 35-44 catechol-O-methyltransferase Mus musculus 115-119 28429453-4 2017 Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis. Tolcapone 114-123 caspase 3 Homo sapiens 267-276 28429453-6 2017 Additionally, COMT was inhibited by siRNA in NB cells and showed similar increases in apoptotic markers compared to Tolcapone. Tolcapone 116-125 catechol-O-methyltransferase Mus musculus 14-18 27388330-8 2016 However, genotype differences emerged after administration of the COMT inhibitor tolcapone: performance of wild-type mice, but not COMT-Met mice, was improved on the 5-choice serial reaction time task after tolcapone administration. Tolcapone 81-90 catechol-O-methyltransferase Mus musculus 66-70 28298647-5 2017 Tolcapone, which is bound with similar high affinity in both TTR binding sites without the usual negative cooperativity, is therefore of interest. Tolcapone 0-9 transthyretin Homo sapiens 61-64 28298647-6 2017 Here we show that TTR fibrillogenesis by the mechano-enzymatic pathway is indeed more potently inhibited by tolcapone than by tafamidis but neither, even in large molar excess, completely prevents amyloid fibril formation. Tolcapone 108-117 transthyretin Homo sapiens 18-21 28066708-3 2017 Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT), reduced delay discounting, a measure of impulsivity, in healthy subjects. Tolcapone 86-95 catechol-O-methyltransferase Homo sapiens 143-171 28066708-3 2017 Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-O-methyltransferase (COMT), reduced delay discounting, a measure of impulsivity, in healthy subjects. Tolcapone 86-95 catechol-O-methyltransferase Homo sapiens 173-177 28066708-5 2017 To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. Tolcapone 69-78 catechol-O-methyltransferase Homo sapiens 54-58 27388330-8 2016 However, genotype differences emerged after administration of the COMT inhibitor tolcapone: performance of wild-type mice, but not COMT-Met mice, was improved on the 5-choice serial reaction time task after tolcapone administration. Tolcapone 207-216 catechol-O-methyltransferase Mus musculus 66-70 27074629-3 2016 Tolcapone and entacapone are potent inhibitors of catechol-O-methyl transferase (COMT) for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 50-79 27445153-11 2016 The COMT inhibitor, tolcapone, increased the DA signal ~2-fold, whereas the DAT inhibitor GBR12909 had no effect. Tolcapone 20-29 catechol-O-methyltransferase Mus musculus 4-8 27089846-1 2016 Tolcapone and entacapone are two potent catechol-O-methyltransferase (COMT) inhibitors with a similar skeleton and displaying similar pharmacological activities. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 40-68 27089846-1 2016 Tolcapone and entacapone are two potent catechol-O-methyltransferase (COMT) inhibitors with a similar skeleton and displaying similar pharmacological activities. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 70-74 27089846-4 2016 The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7, UGT1A9 and UGT1A10. Tolcapone 35-44 UDP glucuronosyltransferase family 1 member A1 Homo sapiens 92-98 27089846-4 2016 The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7, UGT1A9 and UGT1A10. Tolcapone 35-44 UDP glucuronosyltransferase family 1 member A7 Homo sapiens 100-106 27089846-4 2016 The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7, UGT1A9 and UGT1A10. Tolcapone 35-44 UDP glucuronosyltransferase family 1 member A9 Homo sapiens 108-114 27089846-4 2016 The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7, UGT1A9 and UGT1A10. Tolcapone 35-44 UDP glucuronosyltransferase family 1 member A10 Homo sapiens 119-126 27463695-1 2016 Recent efforts have been focused on the development of centrally active COMT inhibitors, which can be valuable assets for neurological disorders such as Parkinson"s disease, due to the severe hepatotoxicity risk associated with tolcapone. Tolcapone 228-237 catechol-O-methyltransferase Rattus norvegicus 72-76 26919286-0 2016 Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice. Tolcapone 56-65 catechol-O-methyltransferase Rattus norvegicus 6-34 26919286-0 2016 Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice. Tolcapone 56-65 catechol-O-methyltransferase Rattus norvegicus 36-40 26919286-0 2016 Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice. Tolcapone 56-65 catechol-O-methyltransferase Rattus norvegicus 162-166 26919286-4 2016 A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. Tolcapone 34-43 catechol-O-methyltransferase Rattus norvegicus 18-22 27089846-5 2016 In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on UGT1A1, UGT1A7, and UGT1A10, while their inhibitory potentials against UGT1A9 were comparable. Tolcapone 27-36 UDP glucuronosyltransferase family 1 member A1 Homo sapiens 81-87 27089846-5 2016 In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on UGT1A1, UGT1A7, and UGT1A10, while their inhibitory potentials against UGT1A9 were comparable. Tolcapone 27-36 UDP glucuronosyltransferase family 1 member A7 Homo sapiens 89-95 27089846-5 2016 In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on UGT1A1, UGT1A7, and UGT1A10, while their inhibitory potentials against UGT1A9 were comparable. Tolcapone 27-36 UDP glucuronosyltransferase family 1 member A10 Homo sapiens 101-108 27089846-6 2016 It is noteworthy that the inhibition constants (Ki) of tolcapone and entacapone against bilirubin-O-glucuronidation in human liver microsomes (HLM) are determined as 0.68muM and 30.82muM, respectively, which means that the inhibition potency of tolcapone on UGT1A1 mediated bilirubin-O-glucuronidation in HLM is much higher than that of entacapone. Tolcapone 55-64 UDP glucuronosyltransferase family 1 member A1 Homo sapiens 258-264 27089846-7 2016 Furthermore, the potential risks of tolcapone or entacapone via inhibition of human UGT1A1 were quantitatively predicted by the ratio of the areas under the plasma drug concentration-time curve (AUC). Tolcapone 36-45 UDP glucuronosyltransferase family 1 member A1 Homo sapiens 84-90 27089846-8 2016 The results indicate that tolcapone may result in significant increase in AUC of bilirubin or the drugs primarily metabolized by UGT1A1, while entacapone is unlikely to cause a significant DDI through inhibition of UGT1A1. Tolcapone 26-35 UDP glucuronosyltransferase family 1 member A1 Homo sapiens 129-135 26582803-2 2016 Inhibitors of COMT, such as tolcapone and entacapone, are used clinically in the treatment of Parkinson"s disease. Tolcapone 28-37 catechol-O-methyltransferase Homo sapiens 14-18 26582803-7 2016 The assay was established using membranes expressing human membrane-bound COMT and was optimized for protein and time to give an acceptable signal window, good potency for tolcapone, and a high degree of translation between data in fluorescence ratio and data in terms of [SAH] produced. Tolcapone 172-181 catechol-O-methyltransferase Homo sapiens 74-78 27074629-3 2016 Tolcapone and entacapone are potent inhibitors of catechol-O-methyl transferase (COMT) for the treatment of Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 81-85 27074629-5 2016 Here, we identified 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) as a possible toxicity-causing off-target of tolcapone, and this protein is not bound by the less toxic COMT inhibitor entacapone. Tolcapone 107-116 3-hydroxyisobutyryl-CoA hydrolase Homo sapiens 20-53 27074629-5 2016 Here, we identified 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) as a possible toxicity-causing off-target of tolcapone, and this protein is not bound by the less toxic COMT inhibitor entacapone. Tolcapone 107-116 3-hydroxyisobutyryl-CoA hydrolase Homo sapiens 55-60 26844013-1 2016 Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors developed as adjunct therapies for treating Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 29-57 26902880-0 2016 Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity. Tolcapone 14-23 transthyretin Homo sapiens 49-62 26902880-4 2016 Here we repurpose tolcapone, an FDA-approved molecule for Parkinson"s disease, as a potent TTR aggregation inhibitor. Tolcapone 18-27 transthyretin Homo sapiens 91-94 26902880-5 2016 Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Tolcapone 0-9 transthyretin Homo sapiens 32-35 26902880-5 2016 Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Tolcapone 0-9 transthyretin Homo sapiens 124-127 26902880-6 2016 Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. Tolcapone 22-31 transthyretin Homo sapiens 51-54 26902880-6 2016 Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. Tolcapone 22-31 transthyretin Homo sapiens 141-144 26902880-6 2016 Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. Tolcapone 22-31 transthyretin Homo sapiens 141-144 26844013-1 2016 Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors developed as adjunct therapies for treating Parkinson"s disease. Tolcapone 0-9 catechol-O-methyltransferase Homo sapiens 59-63 26213577-0 2015 The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice. Tolcapone 44-53 catechol-O-methyltransferase Mus musculus 4-32 26138444-7 2015 Remarkably, our data show that blocking fibril growth by treatment with known pharmacological inhibitor of alpha-syn fibrillization (Tolcapone) or replacing monomeric alpha-syn by monomeric beta-synuclein in alpha-syn mixture composition prevent alpha-syn-induced toxicity in both neuroblastoma cell lines and hippocampal primary neurons. Tolcapone 133-142 synuclein alpha Homo sapiens 107-116 26037113-0 2015 Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. Tolcapone 54-63 catechol-O-methyltransferase Homo sapiens 14-43 26037113-0 2015 Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. Tolcapone 54-63 catechol-O-methyltransferase Homo sapiens 45-49 26037113-0 2015 Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. Tolcapone 54-63 microtubule associated protein 2 Homo sapiens 87-119 26037113-0 2015 Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. Tolcapone 54-63 microtubule associated protein 2 Homo sapiens 121-125 26037113-0 2015 Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. Tolcapone 54-63 synaptophysin Homo sapiens 131-144 26037113-0 2015 Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. Tolcapone 54-63 synaptophysin Homo sapiens 146-149 26037113-1 2015 This investigation aimed to assess whether inhibition of cathecol-O-methyl transferase (COMT) by tolcapone could provide neuroprotection against HIV-associated neurodegenerative effects. Tolcapone 97-106 catechol-O-methyltransferase Homo sapiens 57-86 26037113-1 2015 This investigation aimed to assess whether inhibition of cathecol-O-methyl transferase (COMT) by tolcapone could provide neuroprotection against HIV-associated neurodegenerative effects. Tolcapone 97-106 catechol-O-methyltransferase Homo sapiens 88-92 26037113-8 2015 A concomitant exposure of tolcapone ameliorated the perturbed expression of MAP2 (p = 0.009) and COMT (p = 0.024) associated with HIV. Tolcapone 26-35 microtubule associated protein 2 Homo sapiens 76-80 26037113-8 2015 A concomitant exposure of tolcapone ameliorated the perturbed expression of MAP2 (p = 0.009) and COMT (p = 0.024) associated with HIV. Tolcapone 26-35 catechol-O-methyltransferase Homo sapiens 97-101 26037113-9 2015 Immunofluorescence revealed a trend reduction of SYP and MAP2 with exposure to HIV and that concomitant exposure of tolcapone increased SYP (p = 0.016) compared to HIV alone. Tolcapone 116-125 synaptophysin Homo sapiens 136-139 26213577-3 2015 Tolcapone (TOL), is a clinically-used COMT inhibitor. Tolcapone 0-9 catechol-O-methyltransferase Mus musculus 38-42 25799918-4 2015 A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Tolcapone 108-117 catechol-O-methyltransferase Rattus norvegicus 91-95 25869243-11 2015 Moreover, tolcapone significantly increased the cumulative bile excretion of SAB from 3% to 40% in the rat. Tolcapone 10-19 SH3-domain binding protein 5 Rattus norvegicus 77-80 25802148-5 2015 Specifically, using the brain penetrant catechol-O-methyl transferase (COMT) inhibitor tolcapone [4, 5], we investigated the causal relationship between dopaminergic mechanisms and two prosocial concerns at the core of a number of widely used economic games: (1) the extent to which individuals directly value the material payoffs of others, i.e., generosity, and (2) the extent to which they are averse to differences between their own payoffs and those of others, i.e., inequity. Tolcapone 87-96 catechol-O-methyltransferase Homo sapiens 71-75 25691908-5 2015 Inflammatory cytokines including TNF-alpha, IL-1beta, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. Tolcapone 152-155 tumor necrosis factor Mus musculus 33-42 25691908-5 2015 Inflammatory cytokines including TNF-alpha, IL-1beta, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. Tolcapone 152-155 interleukin 1 beta Mus musculus 44-52 25691908-5 2015 Inflammatory cytokines including TNF-alpha, IL-1beta, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. Tolcapone 152-155 interleukin 6 Mus musculus 58-62 25074639-4 2015 To directly test this association and to evaluate additional behavioral characteristics, including perceived locus of control (LOC), here we used the COMT inhibitor tolcapone in a randomized, double-blind, counterbalanced, within-subject study of 66 subjects genotyped for the Val158Met allele to assess the hypothesis that reducing COMT enzymatic activity interacts with genotype to increase uncertainty-driven exploration. Tolcapone 165-174 catechol-O-methyltransferase Homo sapiens 150-154 24148818-2 2014 Entacapone and tolcapone, COMT inhibitors, are used to mitigate the symptoms of Parkinson"s disease. Tolcapone 15-24 catechol-O-methyltransferase Homo sapiens 26-30 24997271-6 2014 This conclusion was supported by an observation of higher concentration of l-DOPA in the incubation medium under perfusion of MBH with Krebs-Ringer solution containing tolcapone, an inhibitor of catechol-O-methyltransferase, and l-leucine than under perfusion with the same solution, but without l-leucine. Tolcapone 168-177 catechol-O-methyltransferase Rattus norvegicus 195-223 25257296-3 2014 METHODS: Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Tolcapone 210-219 catechol-O-methyltransferase Rattus norvegicus 164-192 25257296-3 2014 METHODS: Working under the hypothesis that reductions in the bioavailability of DA play an integral role in the expression of the excessive drinking phenotype, the catechol-O-methyltransferase (COMT) inhibitor tolcapone was used as a means to amplify cortical DA concentration and drinking behaviors were then assessed. Tolcapone 210-219 catechol-O-methyltransferase Rattus norvegicus 194-198 24148818-9 2014 In conclusion, the combination of EGCG and entacapone/tolcapone synergistically inhibited the growth of lung cancer cells in culture, and the mechanistic basis for this synergy is likely due in part to inhibition of COMT with resultant increase in the levels of unmetabolized EGCG. Tolcapone 54-63 catechol-O-methyltransferase Homo sapiens 216-220 23543593-0 2013 Inhibition of Comt with tolcapone slows progression of polycystic kidney disease in the more severely affected PKD/Mhm (cy/+) substrain of the Hannover Sprague-Dawley rat. Tolcapone 24-33 catechol-O-methyltransferase Rattus norvegicus 14-18 23794107-4 2013 OBJECTIVE: In this study, we explored the effect of tolcapone, a CNS penetrant COMT inhibitor that increases cortical dopamine levels, on brain activity during a Variable Attentional Control (VAC) task. Tolcapone 52-61 catechol-O-methyltransferase Homo sapiens 79-83 23794107-11 2013 While there was no significant effect of tolcapone on these behavioral measures, the neuroimaging data showed a significant effect on load-related changes in dCC, with significantly lower dCC activation on tolcapone compared with placebo. Tolcapone 206-215 frazzled Drosophila melanogaster 188-191 24465516-7 2014 The methylation was reversed by tolcapone, a potent COMT inhibitor, in a dose-dependent manner. Tolcapone 32-41 catechol-O-methyltransferase Rattus norvegicus 52-56 24095246-2 2013 The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson"s disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. Tolcapone 50-59 catechol-O-methyltransferase Homo sapiens 4-32 24095246-2 2013 The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson"s disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. Tolcapone 50-59 catechol-O-methyltransferase Homo sapiens 34-38 24095246-2 2013 The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson"s disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. Tolcapone 50-59 catechol-O-methyltransferase Homo sapiens 191-195 23953269-0 2013 A proof of concept study of tolcapone for pathological gambling: relationships with COMT genotype and brain activation. Tolcapone 28-37 catechol-O-methyltransferase Homo sapiens 84-88 23953269-4 2013 The objective of this study was to determine whether tolcapone, a COMT inhibitor, improves symptoms of PG and to explore whether such effects are dependent on COMT val-158-met polymorphism status and relate to concomitant changes in fronto-parietal activation. Tolcapone 53-62 catechol-O-methyltransferase Homo sapiens 66-70 23543593-6 2013 A 3-month treatment with tolcapone, a selective inhibitor of Comt, was carried out in PKD/Mhm and PKD/US (cy/+) animals. Tolcapone 25-34 catechol-O-methyltransferase Rattus norvegicus 61-65 23543593-10 2013 CONCLUSIONS: Comt has been confirmed to be the first reported modifier gene for PKD and tolcapone offers a promising drug for treating PKD. Tolcapone 88-97 catechol-O-methyltransferase Rattus norvegicus 13-17 22551521-9 2012 In S-adenosyl methionine- and GSH-supplemented human S9 incubations, M1-1 formation decreased by 80% but increased after tolcapone-inhibited catechol-O-methyltransferase (COMT) activity. Tolcapone 121-130 catechol-O-methyltransferase Homo sapiens 141-169 23567203-3 2013 We used the COMT inhibitor, tolcapone, to assess the role of COMT activity in regulating the differential effects of the dopamine releaser, amphetamine (AMPH), on PPI in SD and LE rats. Tolcapone 28-37 catechol-O-methyltransferase Rattus norvegicus 12-16 23567203-7 2013 DISCUSSION: The impact of COMT inhibition on AMPH-modified PPI was categorically different in strains exhibiting low vs. high levels of forebrain Comt expression, consistent with reports in humans that tolcapone has opposite effects on PPI among individuals with polymorphisms conferring low vs. high COMT activity. Tolcapone 202-211 catechol-O-methyltransferase Homo sapiens 26-30 23567203-7 2013 DISCUSSION: The impact of COMT inhibition on AMPH-modified PPI was categorically different in strains exhibiting low vs. high levels of forebrain Comt expression, consistent with reports in humans that tolcapone has opposite effects on PPI among individuals with polymorphisms conferring low vs. high COMT activity. Tolcapone 202-211 catechol-O-methyltransferase Homo sapiens 146-150 23613951-5 2013 Here, we investigated the effect of acute systemic administration of the brain-penetrant COMT inhibitor tolcapone on tissue levels of dopamine, noradrenaline, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Tolcapone 104-113 catechol-O-methyltransferase Rattus norvegicus 89-93 23613951-13 2013 Furthermore, they suggest that the impact of tolcapone may be greater in females than males, a finding which may be of clinical significance in terms of the efficacy and dosing of COMT inhibitors. Tolcapone 45-54 catechol-O-methyltransferase Rattus norvegicus 180-184 22074909-5 2012 Additionally, we examined the effect of pretreatment with the COMT inhibitor tolcapone on acute effects of this cannabinoid on sensorimotor gating in C57BL/6 mice. Tolcapone 77-86 catechol-O-methyltransferase Mus musculus 62-66 22551521-9 2012 In S-adenosyl methionine- and GSH-supplemented human S9 incubations, M1-1 formation decreased by 80% but increased after tolcapone-inhibited catechol-O-methyltransferase (COMT) activity. Tolcapone 121-130 catechol-O-methyltransferase Homo sapiens 171-175 22764248-5 2012 To test this hypothesis directly, we performed a randomized, double-blind, counterbalanced, placebo-controlled study in which we administered the brain penetrant catechol-O-methyltransferase inhibitor tolcapone or placebo to healthy subjects performing a delay discounting task. Tolcapone 201-210 catechol-O-methyltransferase Homo sapiens 162-190