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Catechol-O-methyl transferase

About: Catechol-O-methyl transferase is a research topic. Over the lifetime, 1646 publications have been published within this topic receiving 87360 citations.


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Journal ArticleDOI
TL;DR: Entacapone improves the pharmacokinetic profile oflevodopa when used in combination with a CR levodopa preparation, as it does with a standard levodOPA preparation.
Abstract: We studied the effect of entacapone, a catechol-O-methyltransferase (COMT) inhibitor, on the pharmacokinetics and metabolism of levodopa after administration of a controlled-release (CR) levodopa-carbidopa preparation (Sinemet CR) in an open, randomized trial in 12 healthy male volunteers. The inhibition of soluble COMT (S-COMT) in red blood cells (RBCs) was also measured. Single graded doses of entacapone (100-800 mg) were administered concomitant with a single oral dose of CR levodopa, or CR levodopa was given without entacapone (control treatment), at least 1 week apart. Plasma concentrations of levodopa, 3-O-methyldopa (3-OMD), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), carbidopa, and entacapone were determined for pharmacokinetic calculations. Entacapone decreased dose-dependently the activity of S-COMT in RBCs with a maximal inhibition of 66% after the highest dose (800 mg). Entacapone increased the area under the plasma concentration-time curve (AUC) of levodopa; the increase was highest (33%) after the 400-mg dose. Entacapone did not influence time to maximal concentration (Tmax) of levodopa. Entacapone was absorbed faster than levodopa from the CR preparation. The AUCs of 3-OMD and HVA decreased and that of DOPAC increased dose-dependently after entacapone, maximally by 69, 38, and 74%, respectively. Higher doses of entacapone (400 mg and 800 mg) decreased the AUC, but not Tmax of carbidopa. Over the dose range studied, entacapone was well tolerated. Entacapone is an effective COMT inhibitor. It improves the pharmacokinetic profile of levodopa when used in combination with a CR levodopa preparation, as it does with a standard levodopa preparation. The results justify further clinical studies with entacapone in combination with CR preparations of levodopa.

70 citations

Journal ArticleDOI
TL;DR: The effect of the COMT val158met polymorphism on frontal regulation of attention under emotional distraction is assessed and genetic contributions to interindividual variability in recruitment of mechanisms that regulate affective processing are identified.
Abstract: Early studies of genetic effects on brain activity have been conducted to investigate primarily either the influence of polymorphisms in dopaminergic genes, especially the catechol-O-methyltransferase (COMT) gene, on prefrontal cognitive processes such as working memory, or that of polymorphisms in the serotonin transporter gene on the amygdala response to threatening stimuli. Here, we address genetic influences on the neural systems underlying cognitive-affective interactions. Specifically, we assess the effect of the COMT val158met polymorphism on frontal regulation of attention under emotional distraction. Healthy volunteers were scanned while performing a house-matching task with affectively negative versus neutral distractors. Effects of val allele load were examined on frontal regions associated with attentional control and emotion regulation, and on parahippocampal regions associated with perception of houses. As we predicted, val load correlated positively with activity in control- and task-related regions during performance under emotional distraction. These findings provide an initial step toward identifying genetic contributions to interindividual variability in recruitment of mechanisms that regulate affective processing.

70 citations

Journal ArticleDOI
TL;DR: These data confirm the clinical efficacy of entacapone-standard Sinemet™ combination and indicate that adding entacAPone to controlled release levodopa preparations might provide a useful treatment option in patients with Parkinson's disease with motor fluctuations.
Abstract: Objectives—Entacapone is a specific, potent, peripherally acting catechol-Omethyltransferase (COMT) inhibitor. It has been shown to improve the bioavailability of plasma levodopa and extend its clinical eVect when used as an adjunct to standard levodopa preparations, but there is little experience of the eVect of entacapone on controlled release levodopa preparations. Methods—A double blind, placebo controlled, single dose, randomised, cross over trial was performed in 14 patients with Parkinson’s disease with motor fluctuations to investigate the clinical eVect of a single dose of entacapone (200 mg) when administered with either standard levodopa-carbidopa (Sinemet™) or controlled release levodopa-carbidopa preparations (Sinemet CR™). Results—When entacapone was administered with standard Sinemet™ the duration of the clinical response to standard Sinemet™ was longer in comparison with the response after placebo (p=0.02). Moreover, in the same patients, entacapone significantly increased the duration of the clinical response to Sinemet CR™ (p=0.05) without prolonging the latency of response or enhancing dyskinesias. Conclusions—These data confirm the clinical eYcacy of entacapone-standard Sinemet™ combination. They also indicate that adding entacapone to controlled release levodopa preparations might provide a useful treatment option in patients with Parkinson’s disease with motor fluctuations. A double blind clinical trial with a chronically administered entacaponeSinemet CR™ combination is, however, required to verify this viewpoint. (J Neurol Neurosurg Psychiatry 2000;68:589‐594)

70 citations

Journal ArticleDOI
TL;DR: Frontotemporal function during verbal generation is modulated by variation in COMT genotype which is altered in schizophrenia, which may reflect the perturbation of central dopamine function associated with the disorder.

70 citations

Journal ArticleDOI
TL;DR: Results concerning MAO and COMT activities are now sufficiently inconsistently characteristic of schizophrenics as to question their clinical applicability and to indicate a need for further critical evaluation.
Abstract: • We assayed activities of monoamine oxidase (MAO) type B in blood platelets and type A (and B) in fibroblasts cultured from punch biopsy specimens of skin, as well as of catechol-Omethyltransferase (COMT) in erythrocytes and fibroblasts. Fibroblasts contained moderate amounts of both forms of MAO (types A and B) found in human brain and large amounts of COMT activity. Activities of both enzymes correlated poorly between fibroblasts and blood cells. Comparing carefully diagnosed chronic schizophrenics with age-matched normal young men, we found no difference in these biochemical variables, nor could we distinguish patients with paranoid symptoms. In contrast, we confirmed markedly lower MAO activities in platelet samples from chronic patients provided by colleagues at the National Institute of Mental Health. Results concerning MAO and COMT activities are now sufficiently inconsistently characteristic of schizophrenics as to question their clinical applicability and to indicate a need for further critical evaluation, with special attention to diagnosis, matching of subjects, and effects of possible spurious environmental variables.

69 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202338
202265
202129
202032
201931
201834