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.

Optimizing levodopa pharmacokinetics with multiple tolcapone doses in the elderly.

Abstract: 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. Methods Thirty-six volunteers from 55 to 75 years old participated in this double-blind, placebo-controlled, ascending multiple-dose study. Tolcapone was studied at dosages of 100, 200, 400, or 800 mg three times daily (t.i.d.) in four sequential groups. Each group consisted of nine participants who had been randomized to receive either placebo (n = 3) or tolcapone (n = 6). Tolcapone or placebo was coadministered with carbidopa and levodopa (25 and 100 mg, respectively) for 7 days. Assessments included tolerability, pharmacokinetics of tolcapone, levodopa, and 3-O-methyldopa, and inhibition of COMT activity in erythrocytes. 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. These effects were similar on days 1 and 7 of treatment. Development of tolerance to COMT inhibition was not observed. Onset of effect was rapid (day 1 of treatment), and the maximum effect on levodopa pharmacokinetics was already observed with 100 or 200 mg tolcapone t.i.d. At these dosages, tolcapone pharmacokinetics were linear and stable; accumulation occurred with 800 mg t.i.d. The combination of tolcapone and carbidopa-levodopa was generally well tolerated, although more nausea and vomiting were observed at higher dosages (400 to 800 mg t.i.d.), particularly in women. Conclusion Tolcapone shows promise as an effective adjunct to levodopa in the treatment of Parkinson's disease. Clinical pharmacology data indicate that the therapeutic regimen should be 100 or 200 mg t.i.d. Clinical Pharmacology & Therapeutics (1997) 62, 300–310; doi:

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa.

Abstract: Background Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess negatively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa.

Association analysis of the COMT/MTHFR genes and geriatric depression: An MRI study of the putamen

Abstract: Objective: Catechol-O-Methyltransferase (COMT) and Methylenetetrahydrofolate reductase (MTHFR) had been reported to relate to depression but with inconsistent results. The basal ganglia are also important in the pathophysiology of affective disorder via connections with limbic system and prefrontal cortex. The authors examined the relationship between an interaction of COMT/ MTHFR polymorphisms and volumes of putamen in depressed and nondepressed elders. Methods: Participants included 170 depressed and 83 nondepressed subjects aged 60 years or older. Subjects completed cross-sectional assessments, including clinical evaluation, brain magnetic resonance imaging (MRI) scan, and COMT Val158Met and MTHFR C677T genotyping. Putamen volumes were measured using 1.5-Tesla whole-body MRI system. Statistical models examined the relationship between COMT/MTHFR genotype, proportional volumes of putamen and depression while controlling for age and sex. Results: After controlling for covariates, depressed subjects with MTHFR C/C, both the right and left putamen have smaller volumes as the number of COMT 158Val increase. The left putamen volumes of depressed subjects with COMT Met/Met are smaller as the number of MTHFR 677T increase compared to nondepressed subjects. Conclusions: Our findings do not support a major role for COMT or MTHFR alone. However, an epigenetic interaction of COMT Val158Met and MTHFR C677T polymorphisms may contribute to putamen volumes differences between depressed and nondepressed subjects. Further studies with a larger sample size are necessary to support a genetically based role for basal ganglia structures in the etiopathogenesis of depression.