Hepatic and extrahepatic metabolism of deprenyl, a selective monoamine oxidase (MAO) B inhibitor, of amphetamines in rats: sex and strain differences.

1. Deprenyl is metabolized by rat liver microsomes into methamphetamine (MAP), amphetamine (AP) and nor-deprenyl, and by lung and kidney microsomes into MAP. 2. Treatment of rats with phenobarbital (PB), but not 3-methyl-cholanthrene (3-MC), resulted in significant increases in hepatic metabolism of deprenyl to MAP and AP, and in a slight increase in the pulmonary metabolism of the drug to MAP. Neither treatment showed any effect on the renal metabolism of deprenyl. 3. The inhibitory effect of deprenyl on monoamine oxidase (MAO) B activity of liver was decreased and increased by pretreatment of rats with PB and SKF 525-A, respectively. However, inhibition by deprenyl of MAO-B activity of extrahepatic tissues was not affected by such treatments, except the lung where PB decreased the potency of the drug. 4. Sex differences in the hepatic metabolism of deprenyl to amphetamines were seen in all three strains of rats, Sprague-Dawley, Wistar and Donryu. However, no sex differences observed in the extrahepatic metabolism of deprenyl. 5. Strain differences were also seen in the metabolism of deprenyl, depending on the tissues and metabolites examined.