INHIBITION OF MONOAMINE-OXIDASE-A BY BETA-CARBOLINE DERIVATIVES

beta-Carbolines are endogenous inhibitors of monoamine oxidase (MAO), The interaction of nine beta-carboline derivatives and four 3,4-dihydr o forms with purified MAO A was investigated. All the compounds tested were reversible competitive inhibitors selective for MAO A, in agreem ent with previous studies on membrane preparations. The oxidation of k ynuramine by MAO A in the presence of the more effective inhibitors sh owed a lag period before reaching the steady state. In general, the 1- methyl and 7-methoxy substituents increased the potency, Harmine, 2-me thylharminium, 2,9-dimethylharminium, and harmaline were the most effe ctive inhibitors of the purified MAO A, with low K-i values of 5, 69, 15, and 48 nM, respectively. The inhibitors interacted with the covale ntly bound flavin to induce distinct spectral changes, the magnitude o f which correlated with the efficacy of the inhibition, The more effec tive inhibitors could be in situ inhibitors of MAO A. (C) 1997 Academi c Press, Inc.