THE EFFECT OF SIDE-CHAIN SUBSTITUTION AT POSITION-2 AND POSITION-3 OFTHE HETEROCYCLIC RING OF N-ACETYLENIC ANALOGS OF TRYPTAMINE AS MONOAMINE-OXIDASE INHIBITORS

N-Acetylenic analogues of tryptamine in which the side chain is locate d at position 2 of the indole ring are compared with those in which th e side chain is located at position 3, in terms of their actions as in hibitors of monoamine oxidases A and B. IC50 values at 0 and 30 min of pre-incubation were determined. Time-dependence and irreversible inhi bition confirmed that all of them behave as mechanism-based inhibitors . The kinetic constants of each inhibition step were determined for bo th monoamine oxidase forms and compared between them. In all cases the first-order rate constants for the covalent adduct formation were sim ilar to inhibitor selectivity which is derived solely from differences in affinities for non-covalent binding to the A and B enzymes. Those compounds where the acetylenic side chain was substituted at position 2 of the heterocyclic ring and selective inhibitors of monoamine oxida se A were more potent than those with the side chain in position 3.