Flavin-containing monooxygenase 1-catalysed N,N-dimethylamphetamine N-oxidation
- Authors
- Lee, S. K.; Kang, M. J.; Jin, C.; In, M. K.; Kim, D. -H.; Yoo, H. H.
- Issue Date
- Sep-2009
- Publisher
- Taylor & Francis
- Keywords
- N,N-dimethylamphetamine (DMA); flavin-containing monooxygenase; N-oxidation; N,N-dimethylamphetamine N-oxide (DMANO)
- Citation
- Xenobiotica, v.39, no.9, pp.680 - 686
- Indexed
- SCOPUS
- Journal Title
- Xenobiotica
- Volume
- 39
- Number
- 9
- Start Page
- 680
- End Page
- 686
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/41809
- DOI
- 10.1080/00498250902998699
- ISSN
- 0049-8254
- Abstract
- 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 mu M, V-max of 7.59 nmol min(-1) mg(-1) protein, and intrinsic clearance of 171 mu l 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.
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