Inhibition of rat brainstem monoamine oxidase activity by CGP 6085 A.
CGP 6085 A [4-(5,6-dimethyl-2-benzofuranyl)piperidine] HCl, a known serotonin inhibitor, also inhibits rat brainstem monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in both in vivo and in vitro experiments. Serotonin (5-HT) deamination by MAO-A is inhibited 35% at a dose of 100 mg/kg i.p. in vivo. Similar experiments show a maximal 20% decrease in phenylethylamine (PEA) deamination by MAO-B at a dosage of 30 mg/kg i.p. Over the range of 0.1 to 10 mg/kg i.p., CGP 6085 A decreases 5-HIAA levels in the brainstem. This in vivo inhibition of MAO activity is confirmed by in vitro experiments. In vitro studies in rat brainstem mitochondrial preparations show a dose-dependent, reversible, inhibition of MAO using tyramine as the substrate for the enzyme reaction. With an in vitro IC50 of 2-3 microM, the potency of CGP 6085 A is comparable to pargyline.
D000818:Animals; D001933:Brain Stem / Q000201:enzymology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D010627:Phenethylamines / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000378:metabolism; D014439:Tyramine / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D010880:Piperidines; C029261:phenethylamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C015613:4-(5,6-dimethyl-2-benzofuranyl)piperidine; D010293:Pargyline; D008995:Monoamine Oxidase; D014439:Tyramine