3-AMINO-1-METHYL-5H-PYRIDO[4,3-B]INDOLE (TRP-P-2) AND OTHER HETEROCYCLIC AMINES AS INHIBITORS OF MITOCHONDRIAL MONOAMINE OXIDASES SEPARATED FROM HUMAN BRAIN SYNAPTOSOMES

Effects of a series of heterocyclic amines on type A and B monoamine oxidases were studied using human brain synaptosomal mitochondria as an enzyme source. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was the most potent inhibitor of the heterocyclic amines examined. It inhibited type A monoamine oxidase in competition with the substrate and the Ki value toward type A was 0.84 ± 0.06 μM, which was about 1/50 of its Km value toward an amine substrate, kynuramine; 46.4 ± 11.4 μM. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was also a potent inhibitor. 3- or 2-Aminopyridoindoles or -imidazoles inhibited both type A and B monoamine oxidase competitively to substrate, but inhibition of type B monoamine oxidase by amines with 2-amino-3-methylimidazol ring was non-competitive. In general, type A monoamine oxidase was more sensitive to these heterocyclic amines than type B; the Ki values toward type A were much smaller than those of type B. Inhibition of type A monoamine oxidase by Trp-P-2 proved to be reversible; the enzyme activity inhibited by Trp-P-2 could be fully recovered by removal of Trp-P-2 by column chromatography with Sephadex G-25. © 1990.