Relative selectivity of different beta-adrenoceptor antagonists for human heart beta 1- and beta 2-receptor subtypes assayed by a radioligand binding technique.

The affinity constants of inhibition (Ki values) for both beta 1- and beta 2-receptor subtypes were determined for four different beta-adrenoceptor antagonists by a radioligand binding technique in a human myocardial membrane preparation. The radioligand was the high affinity antagonist [125I]-(-)-iodocyanopindolol (ICYP), and the drugs tested were atenolol, metoprolol, ICI 141,292 and ICI 118,551. Different concentrations of the drugs at test were allowed to compete with a constant concentration of ICYP for the specific binding sites (beta-receptors). Ki values for beta 1- and beta 2-receptors for each beta-adrenoceptor antagonist were developed from these data by computer calculations. Atenolol and metoprolol were found to differ slightly regarding potency (absolute Ki values) and to be practically equal regarding relative selectivity (approx. 40; i.e. ratio between high and low Ki values), while ICI 141,292 was found to have slightly higher relative selectivity (approx. 60) and much higher potency. All these drugs exhibited highest affinity for the beta 1-receptor population. In contrast, ICI 118,551 exhibited a very high relative selectivity (approx. 300) with highest affinity for the beta 2-receptor subtype. The method represents a good supplement to physiological and clinical examinations of selectivity of beta-blockers, and offers several advantages regarding simplicity, specificity and accuracy.