While specific antagonists of the β1-adrenoceptor, such as atenolol and betaxolol, are widely available, a potent specific antagonist selective for the β2-adrenoceptor has yet to be described. Previously described β2-selective antagonists such as butoxamine, H 35/25, and IPS 339 are lacking in potency, specificity, or appropriate β2-selectivity. ICI 118,551 [erythro-dl-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] possesses a high degree of selectivity and specificity for the β2-adrenoceptor. The affinity of propranolol and ICI 118,551 for β-adrenoceptors has been determined by comparing their antagonist potencies, expressed as pA2 values, against the actions of isoproterenol on the guinea pig atrium and uterus. ICI 118,551 had a higher affinity for the uterine β2-receptor than did propranolol (pA2 9.26 and 8.64, respectively) but a lower affinity for the atrial β1- receptor (pA2 7.17 and 8.30, respectively). Thus, the β2/β1-selectivity ratios, in vitro, were 123 for ICI 118,551 and 2.2 for propranolol. The potency and selectivity of ICI 118,551 and atenolol on the chronotropic and vasodilator actions of isoproterenol were compared in anaesthetised dogs. The apparent K'B values at the vascular β-adrenoceptor were 2.1 μg/kg for ICI 118,551 and 253 μg/kg for atenolol, and the potency ratio for antagonism of vascular versus atrial actions of isoproterenol was > 250:1. In regard to ancillary pharmacological properties, ICI 118,551 has no partial agonist activity but has a membrane-stabilising action similar to that of propranolol.
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