Topic
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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TL;DR: A lack of S-COMT has a notable, albeit small, brain-area and sex-dependent effect on the O-methylation of dopamine and 3,4-dihydroxyphenylacetic acid in the mouse brain and induces subtle changes in mouse social interaction behaviors and nociception.
Abstract: Catechol-O-methyltransferase (COMT) has soluble (S-COMT) and membrane bound (MB-COMT) isoforms Our aims were to assess the behavioral phenotype of S-COMT mutant mice and to clarify the role of MB-COMT in dopamine metabolism in different brain areas Behavioral phenotype of the S-COMT mutant mice was assessed using a test battery designed to describe anxiety phenotype, spontaneous locomotor activity, sensorymotor gating, social behavior, and pain sensitivity Microdialysis was used to explore the effect of S-COMT deficiency on extracellular dopamine under an L-dopa load (carbidopa /L-dopa 30/10 mg/kg ip) In behavioral tests, mature adult S-COMT mutants that only possessed MB-COMT exhibited enhanced acoustic startle without alterations in sensorimotor gating They also showed barbering of vibrissae and nonaggressive social dominance, suggesting a change in their social interactions In addition, S-COMT deficiency slightly and sex-dependently affected spinal pain reflex and the effect of morphine on hot-plate latency In microdialysis studies under L-dopa load, S-COMT mutants of both sexes had higher accumbal dopamine levels, but male S-COMT mutant mice showed paradoxically lower prefrontal cortical dopamine concentrations than wild-type animals S-COMT deficiency induced the accumulation of 3,4-dihydroxyphenylacetic acid in all brain areas, which was accentuated after L-dopa loading The lack of S-COMT decreased extracellular homovanillic acid levels However, after L-dopa loading, homovanillic acid concentrations in the prefrontal cortex of S-COMT mutants were similar to those of wild-type mice A lack of S-COMT has a notable, albeit small, brain-area and sex-dependent effect on the O-methylation of dopamine and 3,4-dihydroxyphenylacetic acid in the mouse brain It also induces subtle changes in mouse social interaction behaviors and nociception
31 citations
TL;DR: The results demonstrate that entacapone is a peripheral COMT inhibitor and support the view that CGP 18014 is mainly a centrally acting inhibitor of O‐methylation.
Abstract: 1. Effects of two new inhibitors of catechol O-methylation (CGP 28014 and entacapone; 30 mg kg-1, i.p.) were compared by means of brain microdialysis in rats treated with L-3,4-dihydroxyphenylalanine (L-dopa)/carbidopa (50/50 mg kg-1, i.p., respectively) or saline. 2. In saline-treated rats, CGP 28014 maximally (max) increased striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) effluxes by 41% and 49%, respectively, whereas homovanillic acid (HVA) levels were decreased by 71%. 3. In the presence of L-dopa/carbidopa, a peripherally active inhibitor of catechol O-methyltransferase (COMT) entacapone had a short-lasting increasing effect on L-dopa efflux. Compared to the effects of L-dopa/carbidopa alone 3-O-methyldopa (3-OMD) levels were effectively reduced (max 79%) by entacapone, but not by CGP 28014. 4. Entacapone, in contrast to CGP 28014, increased striatal dopamine efflux (max 492% of that after L-dopa/carbidopa alone). Also DOPAC levels were increased by entacapone (255% at 180 min), but not significantly by CGP 28014 (159% at 180 min). 5. Both compounds initially decreased HVA efflux. The effect of CGP 18014 was longer-lasting. By the end of the measurement, entacapone even increased HVA levels (max 259%). 6. Our results demonstrate that entacapone is a peripheral COMT inhibitor and support the view that CGP 18014 is mainly a centrally acting inhibitor of O-methylation.
31 citations
TL;DR: Evidence of genetic factors potentially affecting human susceptibility to the toxic effects of mercury and other environmental chemicals is extended, and consistent and significant associations were found between increased symptoms and the COMT polymorphism involving the double allelic substitution.
Abstract: Associations were evaluated between a functional single nucleotide polymorphism (Val158Met) in the gene encoding the catecholamine catabolic enzyme catechol O-methyltransferase (COMT), dental mercury exposure, and self-reported symptoms and mood among 183 male dentists and 213 female dental assistants. Self-reported symptoms, mood, and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index for all subjects was created from the work histories. COMT polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups and six self-reported mood factors were evaluated with respect to recent and chronic mercury exposure and COMT polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health pro...
31 citations
Bial1
TL;DR: BIA 3-202 behaves as a reversible, potent and fast tight-binding COMT inhibitor that acts competitively at the substrate binding site of rat liver soluble COMT.
31 citations
TL;DR: Normal or increased levels of urinary dopamine are found in the majority of AADC-deficient patients, which can neither be explained by genotype/phenotype correlations nor by alternative metabolic pathways, although small amounts of dopamine may be formed via tyramine hydroxylation by renal CYP2D6.
31 citations