Trifluoperazine and chlorpromazine antagonize alpha sub(1)- but not alpha sub(2)-adrenergic effects

• Published in: Molecular pharmacology Vol. 23; no. 1; pp. 67 - 70
• Main Authors: Huerta-Bahena, J, Villalobos-Molina, R, Garcia-Sainz, JA
• Format: Journal Article
• Language: English
• Published: 01.01.1983
• Subjects: adipocytes; alpha 1-adrenergic; alpha 2-adrenergic; chlorpromazine; hamsters; hepatocytes; rats; trifluoperazine
• ISSN: 0026-895X

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