Showing papers on "Catechol-O-methyl transferase published in 1987"
TL;DR: Lower enzyme activity in patients with major depression, recurrent and bipolar disorder, depressed, but no change was found in dysthymic disorder when compared to control values, and there was no relationship between COMT activity and age, anxiety and depression scores of patients.
Abstract: Erythrocyte catechol-O-methyltransferase (COMT) activity was measured in normal and depressed populations before specific medication. In the groups of patients, anxiety and depression scores were evaluated by the AMDP rating scale. The authors found lower enzyme activity in patients with major depression, recurrent and bipolar disorder, depressed, but no change was found in dysthymic disorder when compared to control values. However, there was no relationship between COMT activity and age, anxiety and depression scores of patients. Furthermore, the subdivision into two subpopulations, one with normal COMT activity and another with lower COMT activity, did not make it possible to assign a role to the enzyme in the severity of depression. The enzyme could, however, be considered as a genetic marker of depressive vulnerability.
44 citations
TL;DR: Penicillins having one or two chlorine atoms at the positions adjacent to the hydroxyl group were found to have greater stability to catechol-O-methyl-transferase (COMT), which resulted in greater efficiency in vivo in experimental Pseudomonas aeruginosa and Escherichia coli infections.
Abstract: The resistance of 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido]-2- phenylacetamido]penicillanic acid (1a) to metabolism by catechol-O-methyl-transferase (COMT) was increased by introduction of the chlorine atom into the catechol moiety. Penicillins (1b-1d) having one or two chlorine atoms at the positions adjacent to the hydroxyl group were found to have greater stability to COMT. This resulted in greater efficiency in vivo in experimental Pseudomonas aeruginosa and Escherichia coli infections. In vitro activities were essentially unchanged.
30 citations
TL;DR: The experiments reveal a new class of COMT inhibitors that may be of pharmacological and mechanistic value and are suggested to be “nonmethylatable” COMT inhibitor because they exist as quinoidal tautomers resembling pyridones or tropolones rather than as catechols.
Abstract: We report that 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine are potent inhibitors of catechol-O-methyltransferase (COMT), but are not apparent substrates for the enzyme in vitro or in vivo. Three dihy-droxy (catecholic) dihydroisoquinolines, including the 1-benzyl (DesDHP) and the 1-methyl (DSAL) analogs, were found to inhibit COMT activity in rat liver supernatant more effectively than the well-known inhibitor, tropolone. Inhibition of O-methylation was uncompetitive with substrate, and O-methylated products of the catecholic dihydroisoquinolines were undetectable. For these in vitro studies, a facile liquid chromatographic assay was developed utilizing as a site-specific substrate, 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline-1 -carboxylate (salsolinol-1-carboxylate). This catechol produces only one phenolic product isomer when incubated with liver supernatant and S-adenosylmethionine. Following central injection of DSAL in rats, inhibition of brain COMT in vivo was indicated by the reduced brain levels of homovanillic acid, but not of 3,4-dihydroxyphenylacetic acid. Furthermore, O-methylated DSAL metabolites could not be detected in brain by liquid or gas chromatography. We suggest that 6,7–dihydroxy-dihydroisoquinolines are “nonmethylatable” COMT inhibitors because they exist as quinoidal tautomers resembling pyridones or tropolones rather than as catechols. Quinoid formation is supported by the fluorescence and ultraviolet spectra for DSAL and its O-methyl derivatives. The experiments reveal a new class of COMT inhibitors that may be of pharmacological and mechanistic value. Additionally, 3,4-dihydroisoquinolines could arise endogenously via oxidation of the 1,2,3,4-tetrahydroisoquinolines which are ingested or produced from cellular catecholamine condensations. However, it is unlikely that dihydroisoquinoline (e.g., DSAL) concentrations necessary to inhibit COMT significantly would be attained via endogenous pathways.
22 citations
TL;DR: Inhibition of COMT, like inhibition of MAO, is able to enhance the central effects of L-dopa, and this principle might be beneficial in the treatment of Parkinson's disease especially if COMT-inhibitors with greater performance can be developed.
Abstract: The effects of a COMT-inhibitor, U-0521, and a MAO-B-inhibitor, 1-deprenyl, on L-dopa-induced circling behaviour were compared in 6-OHDA-lesioned rats. The actions of U-0521 and 1-deprenyl on the anti-cataleptic effect of L-dopa were also studied. Both U-0521 and 1-deprenyl were found to potentiate L-dopa-induced circling behaviour and anti-cataleptic effect of L-dopa. In both test systems the L-dopa potentiation of 1-deprenyl was longer-lasting than that caused by U-0521. Thus inhibition of COMT, like inhibition of MAO, is able to enhance the central effects of L-dopa. This principle might be beneficial in the treatment of Parkinson's disease especially if COMT-inhibitors with greater performance can be developed.
14 citations
TL;DR: Activities of PNMT and COMT in the rat pineal gland, various hypothalamic nuclei, and the auricular and ventricular myocardia are herein reported.
10 citations
TL;DR: The pattern of localization of COMT and catecholestrogen in the parotid gland of the rat suggests a functional relationship between COMT, and the presence of specific immunoreactive deposits for COMT in the cytoplasm of duct cells, but only those forCOMT in myo-epithelial cells.
Abstract: Catechol-O-methyltransferase (COMT) (EC 2.1.1.6) and catecholestrogen were localized in the parotid gland of the rat by immunocytochemical methods. Specific immunoreactive deposits for COMT and catecholestrogen were found in the cytoplasm of duct cells, but only those for COMT in myo-epithelial cells. The pattern of localization of COMT and catecholestrogen in the parotid gland suggests a functional relationship between COMT and catecholestrogen.
4 citations