In vitro measurement of the beta-adrenergic blocking properties of ORF 12592, the 5-hydroxy analog of propranolol.
ORF 12592 caused concentration-dependent inhibition of isoproterenol stimulated adenylate cyclase activity in sarcolemma-enriched membrane preparations of guinea-pig myocardium. Its potency was slightly less than that of d,l-propranolol. ORF 12592 did not stimulate basal enzyme activity, suggesting it to be devoid of intrinsic sympathomimetic activity. It produced no marked inhibition of basal activity, nor did it inhibit sodium fluoride stimulated enzyme activity, indicating that the compound acts at the receptor rather than the catalytic site of the beta-adrenergic receptor-adenylate cyclase complex. ORF 12592 competed for binding of 3H-dihydroalprenolol to specific beta1 and beta2-adrenergic binding sites on turkey and leopard frog erythrocyte membranes respectively. Concentration-binding inhibition curves indicated that ORF 12592 is a non-selective beta-blocker with slightly less affinity for each beta-adrenergic receptor than propranolol.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000319:Adrenergic beta-Antagonists; D000818:Animals; D001001:Anura; D001667:Binding, Competitive; D004912:Erythrocytes / Q000378:metabolism; D066298:In Vitro Techniques; D011433:Propranolol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011894:Rana pipiens; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012508:Sarcolemma / Q000201:enzymology; D014422:Turkeys
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C013774:ORF 12592; D011433:Propranolol; D000262:Adenylyl Cyclases