THE MONOAMINE OXIDASES OF BRAIN: SELECTIVE INHIBITION WITH DRUGS AND THE CONSEQUENCES FOR THE METABOLISM OF THE BIOGENIC AMINES

Abstract

Two types of monoamine oxidase were identified in vivo in rat brain. These enzymes, designated as type A and type B, were inhibited differentially by the drugs clorgyline (inhibitor of type A enzyme) and deprenyl (inhibitor of type B enzyme). With these drugs, we have shown that the two types of enzyme are responsible for the metabolism of different amines in vivo and that the metabolism of the amines can be altered selectively by administration of these drugs. For example, norepinephrine and serotonin were perferred substrates for type A enzyme and injection of clorgyline induced an elevation of these amines in brain. β-Phenylethylamine was a preferred substrate for type B enzyme and injection of deprenyl slowed the metabolism of β-phenylethylamine in brain. In contrast to the aforementioned amines, dopamine was a substrate for both enzymes and injection of either drug resulted in elevated dopamine concentrations. From our studies, we postulate that it may be possible to alter selectively the metabolism of the putative transmitter amines in man by administration of monoamine oxidase inhibitor drugs that preferentially inactivate a specific type of monoamine oxidase.