p-Methoxyamphetamine, a potent reversible inhibitor of type-A monoamine oxidase in vitro and in vivo

Abstract

P-Methoxyamphetamine [MA] is over 20 .times. as potent as (+)-amphetamine [AP] as an inhibitor of 5-hydroxytryptamine oxidation by monoamine oxidase [MAO] in mouse brain in vitro, with a Ki value of 0.22 .mu.M. It is highly selective towards A-type MAO and possesses only weak activity against the B-type enzyme (Ki value about 500 .mu.M with benzylamine as substrate and solubilized rat liver mitochondria as enzyme source). It is 10 .times. more active than (+)-AP in protecting mouse brain MAO from inhibition by phenelzine in vivo. o-MA and m-MA inhibit MAO both in vitro and in vivo with potencies comparable with, or less than that of (+)-AP.