Regression analysis of the relationship between physical properties and the in vitro inhibition of monoamine oxidase by propynylamines.

Regression analysis of the potency of inhibition of monoamine oxidase by 47 propynylamines revealed that there are three determinants of inhibitory potency: (1) the smallest substituent on the nitrogen must be methyl or hydrogen in order for any activity to be observed; (2) potency is parabolically related to pKa-the optimum pKa is 6.2; and (3) ortho-substituted benzylamine analogs are ten times more potent than predicted on the basis of pKa values. The optimum pKa cannot be explained by differences in fraction ionized but rather in terms of the multistep sequence whereby these compounds inhibit MAO. A very slight positive effect of hydrophobicity on potency was found. The potency of several analogs not included in the original analysis was predicted.