IRREVERSIBLE INHIBITION OF RAT-LIVER MITOCHONDRIAL MAO-A AND MAO-B BY ENANTIOMERS OF DEPRENYL AND ALPHA-METHYLPARGYLINE

Using rat liver mitochondrial monoamine oxidase (MAO) A and MAO B, the possible influence of stereochemical factors upon the irreversible inhibition by propargylamine derivatives has been studied using the enantiomers of deprenyl and of alpha-methylpargyline. Whether studying the inhibition of MAO A or MAO B, little difference was found among enantiomeric pairs in the first-order rate constant (k(2)) for formation of the enzyme inhibitor adduct. Similarly, and with the exception of (S)-D-(+)-deprenyl (k(2) = 0 or an extremely low value at MAO A), the computed value of k(2) for the individual enantiomers showed little variation between MAO A and MAO B. These results suggest that inhibitor selectivity towards a particular form of the enzyme is determined predominantly at the competitive phase of the inhibition.