Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers

L. Y. Lin, Y. Kumagai, A. Hiratsuka, S. Narimatsu, T. Suzuki, Y. Funae, E. W. Distefano, A. K. Cho

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The 4-hydroxylation of S(+)- and R(-)-methamphetamine by rat liver microsomes was examined in Sprague-Dawley and Dark Agouti strains to determine the role of cytochrome P4502D (CYP2D) subfamily isozymes in catalyzing the reaction. In the study, anti-P450-BTL IgG, bufuralol, and quinine, a substrate and inhibitors of CYP2D isozymes, respectively, were found to block ~90% of the reaction as catalyzed by microsomes from Sprague- Dawley rats. Reconstituted systems of CYP2D isozymes purified from rat liver microsomes also mediated the reaction. These observations and the minimal activity found in microsomes from Dark Agouti rats support the notion that methamphetamine, like other phenylisopropylamine compounds, is oxidized on the 4-position of the aromatic ring by CYP2D isozymes.

Original languageEnglish
Pages (from-to)610-614
Number of pages5
JournalDrug Metabolism and Disposition
Volume23
Issue number6
Publication statusPublished - 1995
Externally publishedYes

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Hydroxylation
Methamphetamine
Enantiomers
Cytochromes
Isoenzymes
Rats
Liver Microsomes
Microsomes
Liver
Quinine
Sprague Dawley Rats
Immunoglobulin G
Substrates
Dasyproctidae

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Lin, L. Y., Kumagai, Y., Hiratsuka, A., Narimatsu, S., Suzuki, T., Funae, Y., ... Cho, A. K. (1995). Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers. Drug Metabolism and Disposition, 23(6), 610-614.

Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers. / Lin, L. Y.; Kumagai, Y.; Hiratsuka, A.; Narimatsu, S.; Suzuki, T.; Funae, Y.; Distefano, E. W.; Cho, A. K.

In: Drug Metabolism and Disposition, Vol. 23, No. 6, 1995, p. 610-614.

Research output: Contribution to journalArticle

Lin, LY, Kumagai, Y, Hiratsuka, A, Narimatsu, S, Suzuki, T, Funae, Y, Distefano, EW & Cho, AK 1995, 'Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers', Drug Metabolism and Disposition, vol. 23, no. 6, pp. 610-614.
Lin LY, Kumagai Y, Hiratsuka A, Narimatsu S, Suzuki T, Funae Y et al. Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers. Drug Metabolism and Disposition. 1995;23(6):610-614.
Lin, L. Y. ; Kumagai, Y. ; Hiratsuka, A. ; Narimatsu, S. ; Suzuki, T. ; Funae, Y. ; Distefano, E. W. ; Cho, A. K. / Cytochrome P4502D isozymes catalyze the 4-hydroxylation of methamphetamine enantiomers. In: Drug Metabolism and Disposition. 1995 ; Vol. 23, No. 6. pp. 610-614.
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