CGP 4718 A, a new potential antidepressant with a dual mode of action.
CGP 4718 A (4-[5-chloro-benzofuranyl-2-]-1-methylpiperidine HCl) was found to inhibit MAO A preferentially in vitro in a competitive manner. Assessment of its in vivo effects by an ex vivo approach showed it to be a relatively weak, reversible inhibitor of MAO A. There were also effects on MAO B but they were inferior by a factor of about 10. The onset of the inhibitory effects in rat liver and brain was rapid, being maximal in about 1 h following administration of CGP 4718 A p.o. The inhibition was of relatively short duration with the effects being undetectable 24 h after treatment. CGP 4718 A also inhibited the reuptake of serotonin (5-HT) in synaptosomes in vitro and ex vivo. Evidence for 5-HT uptake inhibition was also found by using the H 75/12 depletor model. Its in vitro and in vivo potency as a 5-HT uptake inhibitor was approximately the same as that of imipramine. The effects on MAO A and on 5-HT uptake occurred over a similar dose range (above 10 mg/kg p.o.) and also had a similar time course. No evidence for inhibitory effects on noradrenaline uptake was found in vivo.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014316:Tritium
D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D014316:Tritium; D012701:Serotonin; C044712:CGP 4718A; D008995:Monoamine Oxidase; D009638:Norepinephrine