Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes
- J Pharmacol Exp Ther. 1998 Feb;284(2):437-42.
- 1. Division of Drug Metabolism, Hokkaido University, Sapporo 060, Japan.
Mequitazine [10-(3-quinuclidinylmethyl) phenothiazine] is a long-acting and selective histamine H1-receptor antagonist that is mainly biotransformed by human liver microsomes to yield hydroxylated and S-oxidized metabolites. Mequitazine hydroxylase was inhibited by propranolol and quinidine. Lineweaver-Burk plots for the hydroxylation and the S-oxidation indicated that the hydroxylation occurred with a low Km (0.72 +/- .26 microM) in human liver microsomes. Microsomes from genetically engineered human B-lymphoblastoid cells expressing Cytochrome P450 2D6 (CYP2D6) efficiently metabolized mequitazine to the hydroxylated and S-oxidized metabolites. The results indicate that CYP2D6 isozyme is a major form of CYP responsible for the metabolism of mequitazine in human liver microsomes. Inhibition of CYP3A-catalyzed midazolam 1'-hydroxylase by various histamine H1 antagonists, including mequitazine, suggested that mequitazine and some Other histamine H1 antagonists could also be inhibitors of CYP3A in human liver microsomes.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Histamine ReceptorResearch Areas: Inflammation/Immunology