Golf S, Bjørnerheim R, Erichsen A, Hansson V
Medical Department B, University Hospital, Oslo, Norway.
Scand J Clin Lab Invest. 1987 Nov;47(7):719-23. doi: 10.1080/00365518709168936.
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.
采用放射性配体结合技术，在人心肌膜制备物中测定了四种不同β肾上腺素能受体拮抗剂对β1和β2受体亚型的抑制亲和常数（Ki值）。放射性配体为高亲和力拮抗剂[125I]-（-）-碘氰吲哚洛尔（ICYP），所测试的药物为阿替洛尔、美托洛尔、ICI 141,292和ICI 118,551。让不同浓度的受试药物与恒定浓度的ICYP竞争特异性结合位点（β受体）。通过计算机计算从这些数据得出每种β肾上腺素能受体拮抗剂对β1和β2受体的Ki值。发现阿替洛尔和美托洛尔在效能（绝对Ki值）方面略有不同，而在相对选择性方面（约40；即高Ki值与低Ki值之比）几乎相等，而ICI 141,292的相对选择性略高（约60）且效能高得多。所有这些药物对β1受体群体表现出最高亲和力。相比之下，ICI 118,551表现出非常高的相对选择性（约300），对β2受体亚型具有最高亲和力。该方法是β受体阻滞剂选择性生理和临床检测的良好补充，在简单性、特异性和准确性方面具有多个优点。
