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 (k2) for formation of the enzyme inhibitor adduct. Similarly, and with the exception of (S)-D-(+)-deprenyl (k2 = 0 or an extremely low value at MAO A), the computed value of k2 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.
Robinson
J B
JB
Faculty of Pharmacy, University of Toronto, Ontario, Canada.
Bocchinfuso
R
R
Khalil
A
A
D000818:Animals; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013237:Stereoisomerism
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D010293:Pargyline