Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes

S. Narimatsu, S. Kariya, S. Isozaki, S. Ohmori, M. Kitada, S. Hosokawa, Y. Masubuchi, T. Suzuki

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Oxidative metabolism of cinnarizine (CZ) and its fluorine derivative flunarizine (FZ), both of which are selective calcium entry blockers, was examined in human liver microsomes. The ring-hydroxylations and the N-desalkylations constituted primary metabolic pathways in microsomal metabolism of CZ and FZ. Among these pathways, the ring-hydroxylase (p-hydroxylation) activities at the cinnamyl moiety of both drugs were highly correlated with debrisoquine 4-hydroxylase activity and CYP2D6 content. Quinidine, a selective inhibitor of CYP2D6, suppressed the ring-hydroxylase activities of CZ and FZ. These results suggest that CYP2D6 is involved in the ring-hydroxylation of the cinnamyl moiety of both CZ and FZ in human liver microsomes.

Original languageEnglish
Pages (from-to)1262-1268
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume193
Issue number3
DOIs
Publication statusPublished - Jun 30 1993
Externally publishedYes

Fingerprint

Cinnarizine
Flunarizine
Cytochrome P-450 CYP2D6
Liver Microsomes
Metabolism
Liver
Hydroxylation
Mixed Function Oxygenases
Quinidine
Fluorine
Metabolic Networks and Pathways
Calcium
Derivatives
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes. / Narimatsu, S.; Kariya, S.; Isozaki, S.; Ohmori, S.; Kitada, M.; Hosokawa, S.; Masubuchi, Y.; Suzuki, T.

In: Biochemical and Biophysical Research Communications, Vol. 193, No. 3, 30.06.1993, p. 1262-1268.

Research output: Contribution to journalArticle

Narimatsu, S, Kariya, S, Isozaki, S, Ohmori, S, Kitada, M, Hosokawa, S, Masubuchi, Y & Suzuki, T 1993, 'Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes', Biochemical and Biophysical Research Communications, vol. 193, no. 3, pp. 1262-1268. https://doi.org/10.1006/bbrc.1993.1761
Narimatsu, S. ; Kariya, S. ; Isozaki, S. ; Ohmori, S. ; Kitada, M. ; Hosokawa, S. ; Masubuchi, Y. ; Suzuki, T. / Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes. In: Biochemical and Biophysical Research Communications. 1993 ; Vol. 193, No. 3. pp. 1262-1268.
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