Involvement of CYP2D6 in oxidative metabolism of cinnarizine and flunarizine in human liver microsomes.
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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.
Biochem Biophys Res Commun. 1993 Jun 30;193(3):1262-8. doi: 10.1006/bbrc.1993.1761.
- PubMed ID
- 8323546 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Cinnarizine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails Flunarizine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails