Phenothiazine drug metabolites: dopamine D2 receptor, alpha 1- and alpha 2-adrenoceptor binding

European Journal of Pharmacology
P A HalsS G Dahl

Abstract

The in vitro binding affinities of levomepromazine, chlorpromazine, fluphenazine, perphenazine and methoxypromazine and their main metabolites to dopamine D2 receptors, alpha 1- and alpha 2-adrenoceptors in rat brain, were examined using [3H]spiperone, [3H]WB 4101 and [3H]yohimbine binding. All compounds had 10-500 times lower affinities to alpha 2-adrenoceptors than to dopamine D2 receptors and alpha 1-adrenoceptors. Ring-hydroxylated and N-demethylated metabolites had relative potencies for dopamine D2 receptor and alpha 1-adrenoceptor binding ranging from 20 to 70%, compared to that of the parent drugs. The ring sulphoxides of levomepromazine, chlorpromazine and perphenazine, except dextro levomepromazine sulphoxide, were virtually inactive in all binding systems. The results indicate that the metabolites having the highest binding affinities for dopamine D2 receptor and alpha 1-adrenoceptor binding may contribute significantly to the therapeutic effect and side-effects of the drugs, and should be measured together with the parent drugs in blood level-effect studies.

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Citations

Jan 1, 1987·Psychopharmacology·E MorelS G Dahl
Jan 1, 1995·European Journal of Drug Metabolism and Pharmacokinetics·P A Hals, S G Dahl
Nov 1, 1988·Biological Psychiatry·O T Osman, R E Becker
Oct 22, 2013·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Satoshi FurukawaAkihiko Sugiyama
Nov 1, 1994·Pharmacology & Toxicology·P A Hals, S G Dahl
Dec 3, 2014·Pharmacological Reports : PR·Jacek WójcikowskiWładysława A Daniel
Jan 29, 2011·Pharmacological Reports : PR·Jacek Wójcikowski, Władysława A Daniel
Jan 10, 2017·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Young Shin JooKi-Wug Sung
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Related Concepts

Metazoa
Metabolic Biotransformation
Brain
Tisercin
August Rats
Alpha-adrenergic receptor
Dopamine Receptor
Antipsychotic Effect
Dopamine D2 Receptor
Rats, Laboratory

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