Flavin-containing monooxygenase 1-catalysed N,N-dimethylamphetamine N-oxidation

Xenobiotica. 2009 Sep;39(9):680-6. doi: 10.1080/00498250902998699.


N,N-dimethylamphetamine (DMA) is a methamphetamine analogue known to be a weaker central nervous system stimulant than methamphetamine. Although a major metabolite of DMA is known to be DMA N-oxide (DMANO), which may be catalysed by flavin-containing monooxygenase (FMO), the specific enzyme(s) involved in this biotransformation has not been identified. In this study, the specific enzyme(s) involved with DMA N-oxidation was characterized by several assays. When DMA was incubated with different human recombinant drug-metabolizing enzymes, including FMOs and cytochrome P450s (CYPs), the formation of DMANO by FMO1 was the most predominant. The Michaelis-Menten kinetic constants for DMA N-oxidation by FMO1 were: K(m) of 44.5 microM, V(max) of 7.59 nmol min(-1) mg(-1) protein, and intrinsic clearance of 171 microl min(-1) mg(-1) protein, which was about twelve-fold higher than that by FMO3. Imipramine, an FMO1-specific inhibitor, selectively inhibited DMA N-oxidation. The resulting data showed that DMA N-oxidation is mainly mediated by FMO1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Imipramine / pharmacology
  • Kinetics
  • Mass Spectrometry
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / chemistry
  • Methamphetamine / metabolism
  • Oxidation-Reduction / drug effects
  • Oxygenases / antagonists & inhibitors
  • Oxygenases / metabolism*


  • Adrenergic Uptake Inhibitors
  • Methamphetamine
  • Cytochrome P-450 Enzyme System
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • dimethylamphetamine
  • Imipramine