MECHANISM OF MONOAMINE OXIDASE-A INHIBITION BY BW-1370U87

BW 1370U87 is a potent, selective inhibitor of rat and human brain MAO -A with a competitive mechanism of action. K(i) = 0.01-mu-M with eithe r serotonin or tyramine as substrate. After preincubation of BW 1370U8 7 with mitochondrial MAO, full enzyme activity was restored by dialysi s. Following oral administration to rats, BW 1370U87 inhibited brain M AO-A in a dose-dependent manner, with a duration greater than 6 hr, bu t less than 24 hr. No significant inhibition of MAO-B by BW 1370U87 wa s observed either in vitro or ex vivo. The selectivity, reversibility, and competitive kinetics of the inhibition by BW 1370U87 may contribu te to an improved safety profile with this novel MAO-A inhibitor.