Stereoselectivity and isoenzyme selectivity of monoamine oxidase inhibitors. Enantiomers of amphetamine, N-methylamphetamine and deprenyl.
The enantiomers of amphetamine, N-methylamphetamine and deprenyl were studied, using a solubilised rat liver mitochondrial monoamine oxidase (MAO) preparation, as competitive inhibitors of MAO-A and MAO-B (5-hydroxytryptamine and beta-phenylethylamine as substrate respectively). Only in the case of deprenyl enantiomers inhibiting MAO-B was a preference shown towards the [R]-configuration enantiomer justifying the use of [R]-(-)-deprenyl (as compared to the racemate) for the specific inhibition of MAO-B. Recalculation of the observed Ki values in terms of the base form of the inhibitor indicated that the activity of all enantiomers fell within a narrow, approximately 25-fold range when inhibiting MAO-B. The selectivity of inhibition of MAO-B by [R]-(-)-deprenyl cannot therefore be attributed to any specific structural features of the MAO-B isoenzyme form but rather to a lack of affinity of this enantiomer towards MAO-A.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology*; D013237:Stereoisomerism
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012642:Selegiline; D008694:Methamphetamine; D000661:Amphetamine