Oxidative metabolism of cinnarizine in rat liver microsomes

Satoru Kariya, Sadao Isozaki, Shizuo Narimatsu, Tokuji Suzuki

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11 Citations (Scopus)

Abstract

The oxidative metabolism of cinnarizine (CZ) [1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine] to 1-(diphenylmethyl)piperazine (M-1), 1-(diphenylmethyl)-4-[3-(4′-hydroxyphenyl)-2-propenyl]piperazine (M-2), benzophenone (M-3) and 1-[(4′-hydroxyphenyl)-phenylmethyl]-4-(3-phenyl-2-propenyl)piperazine (M-4) has been studied in rat liver microsomes. In Wistar rats, kinetic analysis revealed sex differences (male > female) in the Km values for formation of all the metabolites and the Vmax values for the formation of M-1, M-3 and M-4. The reactions required NADPH, and were inhibited by carbon monoxide and SKF 525-A. Only M-2 formation was suppressed by sparteine or metoprolol, and was significantly lower in female Dark Agouti rats than in Wistar rats of both sexes. The results suggest that CZ is oxidized by cytochrome P450, and M-2 formation is related to debrisoquine/sparteinetype polymorphic drug oxidation.

Original languageEnglish
Pages (from-to)1471-1474
Number of pages4
JournalBiochemical Pharmacology
Volume44
Issue number7
DOIs
Publication statusPublished - Oct 6 1992

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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