PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
11793426-1	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
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
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
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
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
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
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
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	49-53
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
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
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	91-95
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
11290879-11	2001	Additional tolcapone reversed the protective effect of COMT.	Tolcapone	11-20	catechol-O-methyltransferase	Homo sapiens	55-59
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
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
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
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
11038168-1	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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
10064789-3	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
10064789-11	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
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
10064789-12	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
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
10064789-10	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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
9578674-1	1998	Tolcapone is a potent, selective, reversible inhibitor of COMT.	Tolcapone	0-9	catechol-O-methyltransferase	Homo sapiens	58-62
9859687-0	1998	[Treatment of Parkinson"s disease with COMT inhibitors: tolcapone].	Tolcapone	56-65	catechol-O-methyltransferase	Homo sapiens	39-43
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	11-21	catechol-O-methyltransferase	Homo sapiens	47-75
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
9404535-0	1996	[COMT inhibition with tolcapone].	Tolcapone	22-31	catechol-O-methyltransferase	Homo sapiens	1-5
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
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
8527287-0	1995	Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa.	Tolcapone	71-80	catechol-O-methyltransferase	Homo sapiens	56-60
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
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
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
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
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
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
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
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
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
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
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
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	77-81
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
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
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
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
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
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
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	55-83
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
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
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
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	90-118
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
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
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
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
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
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
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
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
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
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
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
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
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
35523943-0	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
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
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
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
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
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
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
33289420-3	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
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
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
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
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
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
32617646-0	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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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	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
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
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
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
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
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
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
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
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
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
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
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
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
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	81-90	catechol-O-methyltransferase	Mus musculus	66-70
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
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
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	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
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
26902880-0	2016	Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity.	Tolcapone	14-23	transthyretin	Homo sapiens	49-62
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
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
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
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
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
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
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
26213577-0	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
26213577-3	2015	Tolcapone (TOL), is a clinically-used COMT inhibitor.	Tolcapone	0-9	catechol-O-methyltransferase	Mus musculus	38-42
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	tumor necrosis factor	Mus musculus	33-42
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	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
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
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
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
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	194-198
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
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
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
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
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
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
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
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
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
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	141-169
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
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
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
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
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
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
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
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
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
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
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
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	38-67
21062636-0	2011	Kleptomania treated with tolcapone, a catechol-O-methyl-transferase (COMT) inhibitor.	Tolcapone	25-34	catechol-O-methyltransferase	Homo sapiens	69-73
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
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
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
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
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
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
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
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
18536698-0	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
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
18536698-11	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
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
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
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
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
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
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
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
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
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