Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects

J Huerta-Bahena, R Villalobos-Molina and JA Garcia-Sainz

Trifluoperazine and chlorpromazine inhibited in a dose-dependent manner the stimulation of glycogenolysis, gluconeogenesis, and ureogenesis due to alpha 1-adrenergic stimulation in rat hepatocytes. In contrast, the antipsychotic agents were unable to block the inhibition of adenylate cyclase due to alpha 2-adrenergic activation in hamster adipocytes. Binding experiments showed that trifluoperazine and chlorpromazine at low concentrations displaced tritiated dihydroergocryptine binding from rat liver membranes (alpha 1-adrenergic sites), whereas very large concentrations of the phenothiazine derivatives were required to displace dihydroergocryptine from hamster adipocyte membranes (alpha 2- adrenergic sites). It is concluded that chlorpromazine and trifluoperazine are much more potent at alpha 1- than at alpha 2- adrenergic receptors. The use of rat hepatocytes and hamster adipocytes to study the alpha-adrenergic subtype selectivity of drugs is proposed.

Volume 23, Issue 1, pp. 67-70, 01/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics