Metabolism of N,N-dialkylated amphetamines, including deprenyl, by CYP2D6 expressed in a human cell line

Xenobiotica. 2000 Mar;30(3):297-306. doi: 10.1080/004982500237686.


1. Five N,N-dialkylated amphetamines, N-methyl-N-propargylamphetamine (deprenyl; DEP), N-benzyl-N-methylamphetamine (benzphetamine; BPA), N-allyl-N-methylamphetamine (AMA), N,N-diallylamphetamine (DAA) and N-methyl-N-propylamphetamine (MPA), were metabolized in vitro with a microsomal preparation from cells expressing human CYP2D6 to determine what influence the N,N-dialkyl substituents had on the extent of N-dealkylation and/or aromatic ring oxidation. 2. The results obtained from experiments with the first two substrates, DEP and BPA, were surprisingly different. Whereas DEP was N-demethylated and N-depropargylated by the CYP2D6 enzyme system, no metabolites were formed from BPA. Subsequently, it was determined that AMA, DAA and MPA also underwent CYP2D6-catalysed N-dealkylation. Both N-methyl- and N-allylamphetamine were identified as products of AMA metabolism; similarly, metabolism of MPA produced both N-methyl- and N-propargylamphetamine, and N-allylamphetamine was the sole metabolite of DAA. 3. No N,N-didealkylated product (i.e. amphetamine) was isolated from incubates of any of the five substrates, and none of the N,N-dialkylated substrates was metabolized to a ring-hydroxylated product. 4. Rates of these CYP2D6-catalysed reactions were dependent on the nature and degree of unsaturation of the N-substituents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / metabolism
  • Amphetamines / metabolism*
  • Benzphetamine / metabolism
  • Cell Line
  • Chromatography, Gas
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Humans
  • Methamphetamine / metabolism
  • Methylation
  • Microsomes / metabolism
  • Models, Chemical
  • Selegiline / metabolism*
  • Transfection


  • Amphetamines
  • N-methyl-N-propyl amphetamine
  • Benzphetamine
  • Selegiline
  • Methamphetamine
  • Amphetamine
  • Cytochrome P-450 CYP2D6