P450 phenotyping of the metabolism of selegiline to desmethylselegiline and methamphetamine.

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Benetton SA, Fang C, Yang YO, Alok R, Year M, Lin CC, Yeh LT

P450 phenotyping of the metabolism of selegiline to desmethylselegiline and methamphetamine.

Drug Metab Pharmacokinet. 2007 Apr;22(2):78-87.

PubMed ID

17495414 [ View in PubMed

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Abstract

Although there is evidence in the literature of the participation of CYP2B6 in the metabolism of selegiline, it is not clear which other CYP isoforms contribute to its metabolism. The aim of this study was to investigate the P450 isozymes (CYPs) involved in the metabolism of selegiline to desmethylselegiline (DMS) and methamphetamine (MA) using four assays: incubation of selegiline with cDNA expressed CYPs, inhibition of DMS and MA formations in human liver microsomes by CYP-selective chemical inhibitors or CYP-specific antibodies, and correlation analysis. Correlation analysis, performed in a bank of 15 individual human liver microsomes, yielded correlation coefficients for DMS and MA formation of 0.769 and 0.792, respectively, for CYP2B6 (p<0.0001) and 0.333 and 0.349, respectively, for CYP3A4 (p<0.05). These results were supported by chemical/specific antibody inhibition assays. The results of correlation analysis and chemical inhibition also indicated that CYP2A6 seems to play a small role in the metabolism of selegiline. These findings confirm that CYP2B6 plays a major role in the metabolism of selegiline and also suggest the involvement of CYP3A4 and CYP2A6.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Selegiline	Cytochrome P450 2A6	Protein	Humans	Unknown	Substrate Inhibitor	Details
Selegiline	Cytochrome P450 2B6	Protein	Humans	Unknown	Substrate Inhibitor	Details
Selegiline	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate	Details