title: Selective inhibition of MAO-A in serotonergic synaptosomes by two amphetamine metabolites, p-hydroxyamphetamine and p-hydroxynorephedrine.
abstract: The present study was carried out mainly to clarify whether the two amphetamine metabolites, p-hydroxyamphetamine (P-OHA) and p-hydroxynorephedrine (p-OHN) are taken up by mouse brain 5-hydroxytryptamine (5-HT) nerve terminals to inhibit type A monoamine oxidase (MAO-A) and then potentiate the abnormal behavior, head-twitch. Of the two metabolites, only intracerebroventricular p-OHA, at 80 ?g/mouse, sufficient to cause a head-twitch response (HTR), appreciably inhibited MAO-A activity without affecting MAO-B activity in homogenates of the mouse striatum, hypothalamus and the rest of the forebrain; and p-OHN did not inhibit either type of MAO at the dose tested. Estimation of intra- and extrasynaptosomal MAO-A activity showed that both metabolites significantly inhibited only the intrasynaptosomal deamination of 5-HT by MAO-A with p-OHA being more potent. Taken together with our previous findings, these present results clearly indicate that p-OHA may accumulate in the 5-HT nerve terminals through the uptake system, and concomitantly inhibit MAO-A activity. These actions of p-OHA may increase intraneuronal 5-HT levels and then potentiate 5-HT release to cause interaction with the post-synaptic 5-HT receptors.
authors.affiliation: Department of Pharmacology, School of Medicine, Showa University, Tokyo 142 Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.lastname: Se Kyungkim
authors.forename: H
authors.initials: H
authors.lastname: Kinemuchi
authors.forename: T
authors.initials: T
authors.lastname: Tadano
authors.forename: S
authors.initials: S
authors.lastname: Satoh
authors.forename: N
authors.initials: N
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Oyama
authors.forename: K
authors.initials: K
authors.lastname: Kisara