Relative selectivity of different β-adrenoceptor antagonists for human heart β₁- and β₂-receptor subtypes assayed by a radioligand binding technique

Abstract

The affinity constants of inhibition (K_i values) for both β₁- and β₂-receptor subtypes were determined for four different β-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 (β-receptors). K_i values for β₁- and β₂-receptors for each β-adrenoceptor antagonist were developed from these data by computer calculations. Atenolol and metoprolol were found to differ slightly regarding potency (absolute K_i values) and to be practically equal regarding relative selectivity (approx. 40; i.e. ratio between high and low K_i 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 β₁-receptor population. In contrast, ICI 118 551 exhibited a very high relative selectivity (approx. 300) with highest affinity for the β₂-receptor subtype. The method represents a good supplement to physiological and clinical examinations of selectivity of β-blockers, and offers several advantages regarding simplicity, specificity and accuracy.

Key words:

• β-adrenergic antagonists
• β-adrenergic receptors
• human heart