Mechanism of monoamine oxidase‐A inhibition by BW 1370U87

BW 1370U87 is a potent, selective inhibitor of rat and human MAO-A with a competitive mechanism of action. Ki = 0.01 μM with either serotonin or tyramine as substrate. After preincubation of BW 1370U87 with mitochondrial MAO, full enzyme activity was restored by dialysis. Following oral administration to rats, BW 1370U87 inhibited brain MAO-A in a dose-dependent manner, with a duration greater than 6 hr, but less than 24 hr. No significant inhibition of MAO-B by BW 1370U87 was observed either in vitro or ex vivo. The selectivity, reversibility, and competitive kinetics of the inhibition by BW 1370U87 may contribute to an improved safety profile with this novel MAO-A inhibitor.