Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects.
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.
D000273:Adipose Tissue / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D006224:Cricetinae; D004088:Dihydroergotoxine / Q000494:pharmacology; D005260:Female; D005943:Gluconeogenesis / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008647:Mesocricetus; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D014268:Trifluoperazine / Q000494:pharmacology*; D014508:Urea / Q000096:biosynthesis
D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D004088:Dihydroergotoxine; D014268:Trifluoperazine; D014508:Urea; D002746:Chlorpromazine