Metabolism of deprenyl, a selective monoamine oxidase (MAO) B inhibitor in rat: relationship of metabolism to MAO-B inhibitory potency.
Deprenyl, a selective inhibitor of monoamine oxidase type B (MAO-B), was metabolized in rats to methamphetamine (MAP), amphetamine (AP) and their corresponding p-hydroxylated metabolites, p-hydroxy-MAP and p-hydroxy-AP. Recovery of metabolites in 24 h urine was 25% of the dose, and there was no urinary excretion of unchanged deprenyl. Deprenyl was converted into MAP, AP and nordeprenyl when incubated in vitro with rat-liver microsomes in the presence of NADPH. This metabolism was inhibited in an atmosphere of N2 and by CO, and by SKF 525-A, but to a lesser extent by methimazole. Liver microsomes from phenobarbital (PB)-treated rats, but not 3-methylcholanthrene (3-MC)-treated rats, stimulated the metabolism of deprenyl in vitro to MAP and AP, but not to nordeprenyl. In contrast, microsomes from SKF 525-A-treated rats showed decreased activity in the metabolism of deprenyl to all three metabolites. The inhibitory effect of the drug on hepatic MAO-B activity was annulled by pretreatment of rats with PB, but not 3-MC, and augmented by pretreatment with SKF 525-A.
Yoshida
T
T
Yamada
Y
Y
Yamamoto
T
T
Kuroiwa
Y
Y
D000661:Amphetamine / Q000378:metabolism; D000818:Animals; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000378:metabolism* / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D012642:Selegiline; D008694:Methamphetamine; D008713:Methimazole; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D000661:Amphetamine; D010634:Phenobarbital