Metabolism of deprenyl, a selective monoamine oxidase (MAO) B inhibitor in rat: relationship of metabolism to MAO-B inhibitory potency

Xenobiotica. 1986 Feb;16(2):129-36. doi: 10.3109/00498258609043515.


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.

MeSH terms

  • Amphetamine / metabolism
  • Animals
  • Chromatography, Gas
  • Cytochrome P-450 Enzyme System / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Hydroxylation
  • In Vitro Techniques
  • Male
  • Methamphetamine / metabolism
  • Methimazole / pharmacology
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / enzymology
  • Monoamine Oxidase Inhibitors*
  • Phenethylamines / metabolism*
  • Phenobarbital / pharmacology
  • Proadifen / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Selegiline / metabolism*
  • Selegiline / pharmacology


  • Monoamine Oxidase Inhibitors
  • Phenethylamines
  • Selegiline
  • Methamphetamine
  • Methimazole
  • Methylcholanthrene
  • Cytochrome P-450 Enzyme System
  • Proadifen
  • Amphetamine
  • Phenobarbital