Biochemical evidence for the dual action of labetalol on alpha- and beta-adrenoceptors.
1 Labetalol (AH 5158A) inhibited the adrenaline-stimulated adenylate cyclase activity of rat liver and heart. This drug had no effect on basal or guanosine triphosphate (GTP)-activated adenylate cyclase activities. 2 Labetalol displaced the binding of the specific ligands [3H]-dihydroergocryptine and (-)-[3H]-dihydroalprenolol from their respective alpha and beta-adrenoceptors in rat heart and liver. The affinity of labetalol was 10 fold higher for the beta- than for the alpha-adrenoceptor. It appeared to be 10 to 100 times less potent than phentolamine in blocking alpha-adrenoceptors and 5 to 10 times less potent than propranolol in blocking beta-receptors. 3 It is concluded that labetalol exerts its dual alpha- and beta-antagonism by acting directly on the plasma membranes, where it binds competitively to alpha- and beta-adrenoceptors.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000526:Alprenolol / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D004088:Dihydroergotoxine / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology*; D008099:Liver / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D004088:Dihydroergotoxine; D000526:Alprenolol; D000262:Adenylyl Cyclases; D007741:Labetalol; D004837:Epinephrine