Inhibition of monoamine oxidase by two substrate-analogues, with different preferences for 5-hydroxytryptamine neurons.

Various intraperitoneal doses of 5-fluoro-alpha-methyltryptamine (5-FMT), given to mice, dose-dependently inhibited only MAOA 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 MAOB activity, with complete recovery within 45 min after the injection. Regardless of the differences in time interval and degree of inhibition of MAOA by 5-FMT or MAOB by p-CMP, both kinds of inhibition were competitive, with respect to oxidation of the respective substrate. 5-Fluoro-alpha-methyltryptamine markedly protected only MAOA against inhibition by phenelzine, without protecting MAOB. 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, MAOB-selective inhibitor and 5-FMT has the same characteristics of selectivity for MAOA in central serotonergic neurons.