Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “COMT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed1995

Acute administration of levodopa-benserazide and tolcapone, a COMT inhibitor, Parkinson's disease.

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. To test this hypothesis, we studied the motor effect induced by three acute administrations of a dose of levodopa-benserazide (Madopar) with either 200 mg or 400 mg of tolcapone or placebo, in a double-blind latin-square design. The duration of the on-phase could be compared in 10 parkinsonian patients suffering from square-shaped motor effect. In comparison to placebo, 200 mg and 400 mg of tolcapone significantly increased the mean duration of the on-phase by 61.7 min ( +/- 19.4 SEM) and by 72.2 min ( +/- 18.5), respectively. This clinical effect is suggested to be related mainly to the increase in levodopa area under the curve and half-life induced by tolcapone. The intensity in dyskinesias was increased by 400 mg of tolcapone. Tolcapone appears to be well tolerated and could be helpful as an adjuvant treatment to levodopa in parkinsonian patients with motor fluctuations.

Aged↗
PubMed2005

Association between the COMT Val158Met polymorphism and propensity to anxiety in an Australian population-based longitudinal study of adolescent health.

OBJECTIVES: Catechol-O-methyltransferase plays a central role in the metabolism of biogenic amines such as norepinephrine, dopamine and serotonin. Functional studies have demonstrated a dose relationship between ValMet genotypes and catechol-O-methyltransferase activity. Compared with the ValVal genotype, the ValMet and MetMet genotypes result in two- and four-fold reductions in catechol-O-methyltransferase activity, respectively. Two recent reports have observed the association between the MetMet genotype and risk of anxiety in adult populations. We examined the association between the ValMet genotypes and propensity to anxiety across adolescence. METHODS: Participants were drawn from an eight-wave study of the mental and behavioural health of over 2000 young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 to present). DNA was received from 962 participants using a cheek swab collection method. RESULTS: The odds of reporting persistent episodic anxiety (phobic avoidance, panic attacks) were doubled among carriers of the MetMet genotype (odds ratio 2.0, 95% confidence interval 1.1-3.4, P=0.014). A dose relationship between additional copies of the Met allele and persistent episodic anxiety was also observed (1.5, 1.1-1.94, P=0.007). Stratification by sex showed that the risk effect of the Met allele was among females only. No association was observed for measures of neuroticism, persistent generalized anxiety, or a composite measure of psychiatric distress. CONCLUSION: These data replicate previous findings suggesting association between the ValMet polymorphism and specific expressions of anxiety among females.

Adolescent↗
PubMed1983

Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness. I. Plasma dopamine-beta-hydroxylase activity in endogenous depression.

On the basis of studies carried out with a group of 47 patients with endogenous depressive illness, lower plasma activity of dopamine-beta-hydroxylase (DBH) was found as compared with a control group (31 healthy persons). Lower DBH activity particularly characterized bipolar patients. Lowest DBH activity was found in patients with a family history of psychiatric disorders, in particular, affective illness (in comparison with the control group the difference was statistically significant, P less than 0.05). It was noticed, that in a period of remission or significant improvement the enzymatic activity increases, although in some cases the level of activity is still lower than in the control group. There was a correlation between activity of the enzyme and clinical course of the illness and susceptibility to antidepressive drugs. Most of the observed phenomena are related to male patients. On the basis of these studies and data supplied by corresponding literature, concerning in particular the effects of DBH inhibitors (fusaric acid, disulfiram), the authors consider that changes in DBH activity may play a role in the pathogenesis of depression and that DBH deserves further studies, also of genetic nature.

Adult↗
PubMed1983

Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness. III. Platelet monoamine oxidase activity in endogenous depression.

Platelet MAO activity was determined in blood from 31 healthy persons and 43 persons with endogenous depressive syndrome. It was found that the enzyme activity is significantly higher in women than in men, both in healthy controls and in affective illness groups. Statistically significant lowering of the enzyme activity was found in the group of women with affective illness as compared with healthy women controls (P less than 0.05). Although the latter phenomenon is true of all three diagnostic subgroups of affective disorder (bipolar, unipolar, undifferentiated), it is most pronounced, and statistically significant only in the group of women with an undifferentiated course of disease. A small rise in the enzyme activity was noticed in some patients during remission, as compared with a period of depression, but this was not statistically significant. Analysis of the possible links between MAO activity and the clinical picture, or the severity of depression, revealed no significant correlations. No correlation was found between the level of MAO activity and a family history of psychiatric disturbances in general, and affective disorders in particular--in either women or in men.

Adult↗
PubMed1994

Effect of entacapone, a COMT inhibitor, on clinical disability and levodopa metabolism in parkinsonian patients.

We studied the effect of entacapone, a selective catechol-O-methyltransferase inhibitor, on the bioavailability and clinical effect of levodopa in Parkinson's disease (PD). On day 1 (control day), nine patients received their own levodopa (plus benserazide) medication only; for the next 7 days they received 200 mg of entacapone with each dose of levodopa (tid or qid). We evaluated disability in the morning (8 AM) before drug administration and then at 1-hour intervals until 6 PM on days 1, 2, and 8, using a modified motor part of the Unified Parkinson's Disease Rating Scale. Repeated blood samples were taken before and during the 4 hours after the morning drugs for pharmacokinetic evaluation of entacapone and of levodopa and its metabolites. Added to the levodopa treatment, entacapone decreased clinical disability by about 16% (p < 0.05) from day 1 to day 8. The area under the curve (AUC) of levodopa increased by 38% (p < 0.01) after administration of a single dose of entacapone and by 40% (p < 0.05) after 7 days of multiple dosing with entacapone. Entacapone did not change the Tmax and Cmax values of levodopa. After 7 days of treatment with entacapone, the AUC of 3-O-methyldopa had decreased by 44% (p < 0.01) and of homovanillic acid by 26% (p < 0.05) as compared with treatment with levodopa alone. Four patients became slightly more dyskinetic during entacapone treatment than before it. The combination of entacapone and levodopa was well tolerated, judged by the lack of significant changes in hemodynamic and safety variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Interspecies scaling of tolcapone, a new inhibitor of catechol-O-methyltransferase (COMT). Use of in vitro data from hepatocytes to predict metabolic clearance in animals and humans.

1. In the present study, in vivo pharmacokinetic data in animals were combined with in vitro metabolic data from animal and human hepatocytes to predict the human systemic plasma clearance and the kinetic profile of tolcapone, a compound metabolized by phase II reactions. 2. The integration of in vitro metabolic data from hepatocytes into allometric scaling gave satisfactory predictions of metabolic clearance in humans for tolcapone (74.2 ml/min predicted versus 118 ml/min observed). 3. Using combined time transformations and in vitro metabolic rates, the range of values predicted from the various animal species (90.4 to 242 ml/min, 0.60 to 2.2 h and 7.3 to 121 for clearance, half-life and volume of distribution, respectively) were in good agreement with the observed values in humans (118 ml/min, 1.3 h and 8.6 h, respectively). 4. Compared to the conventional correction factors (e.g. maximum life span, brain weight), in vitro metabolic data provide a more rational basis for extrapolating the metabolic clearance in humans.

Animals↗
PubMed1999

[COMT inhibitors].

Explore the source record for details and available documents.

Antiparkinson Agents↗