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

Shizuo Narimatsu; Satoru Kariya; Sadao Isozaki; Shlgeru Ohmori; Mitsukazu Kitada; Shin Hosokawa; Yasuhlro Masubuchi; Tokuji Suzuki

doi:10.1006/bbrc.1993.1761

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

Shizuo Narimatsu, Satoru Kariya, Sadao Isozaki, Shlgeru Ohmori, Mitsukazu Kitada, Shin Hosokawa, Yasuhlro Masubuchi, Tokuji Suzuki

Research output: Contribution to journal › Article › peer-review

31 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 language	English
Pages (from-to)	1262-1268
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	193
Issue number	3
DOIs	https://doi.org/10.1006/bbrc.1993.1761
Publication status	Published - Jun 30 1993
Externally published	Yes

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "Involvement of CYP2D6 in Oxidative Metabolism of Cinnarizine and Flunarizine in Human Liver Microsomes",

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.",

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AU - Narimatsu, Shizuo

AU - Kariya, Satoru

AU - Isozaki, Sadao

AU - Ohmori, Shlgeru

AU - Kitada, Mitsukazu

AU - Hosokawa, Shin

AU - Masubuchi, Yasuhlro

AU - Suzuki, Tokuji

PY - 1993/6/30

Y1 - 1993/6/30

N2 - 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.

AB - 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.

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

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