Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine

A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.