Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes.

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Nakamura K, Yokoi T, Kodama T, Inoue K, Nagashima K, Shimada N, Shimizu T, Kamataki T

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.

PubMed ID

9454781 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drugs

Mequitazine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mequitazine	Histamine H1 receptor	Protein	Humans	Yes	Antagonist	Details

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Mequitazine	Cytochrome P450 2D6	Protein	Humans	Unknown	Substrate	Details
Mequitazine	Cytochrome P450 3A4	Protein	Humans	Unknown	Inhibitor	Details

Drug Interactions

Drugs	Interaction
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