INHIBITION OF MONOAMINE-OXIDASE BY 2 SUBSTRATE-ANALOGS, WITH DIFFERENT PREFERENCES FOR 5-HYDROXYTRYPTAMINE NEURONS

Various intraperitoneal doses of 5-fluoro-alpha-methyltryptamine (5-FMT), given to mice, dose-dependently inhibited only MAO(A) activity, with similar degrees of inhibition in the striatum, hypothalamus and the rest of the forebrain. The activity inhibited in these regions, completely recovered to control levels within 24 hr after the injection. In contrast, p-chloro-beta-methylphenethylamine (p-CMP), selectively inhibited MAO(B) activity, with complete recovery within 45 min after the injection. Regardless of the differences in time interval and degree of inhibition of MAO(A) by 5-FMT or MAO(B) by p-CMP, both kinds of inhibition were competitive, with respect to oxidation of the respective substrate. 5-Fluoro-alpha-methyltryptamine markedly protected only MAO(A) against inhibition by phenelzine, without protecting MAO(B). Also, 5-FMT greatly increased one kind of animal behaviour, the head-twitch and this behaviour was greatly reduced by treatment with fluoxetine, but increased by reserpine. The results indicate that p-CMP is a short-acting, probably reversible, MAO(B)-selective inhibitor and 5-FMT has the same characteristics of selectivity for MAO(A) in central serotonergic neurons.