Kiyingi K S, Temple D M
Arch Int Pharmacodyn Ther. 1983 Jul;264(1):59-72.
A study has been carried out to establish the best method for determining the cardioselectivity of beta-adrenoceptor antagonists in vivo, exemplified by atenolol in the anaesthetized cat preparation. Using three beta-adrenoceptor agonists: terbutaline (beta 2), dobutamine (beta 1), and isoprenaline and monitoring atenolol's antagonism of the agonist effects on heart rate, airway elastance and soleus muscle tension, parallel shifts in dose-response curves for each agonist were observed on each parameter. The cardioselectivity of atenolol was determined with each agonist by comparison of DR10 values from Schild plots and mean dose-ratio shifts. It is concluded that the cardioselectivity of atenolol is best determined by comparing its antagonism of dobutamine (beta 1) on heart rate (beta 1) with its antagonism of terbutaline (beta 2) on soleus muscle tension (beta 2) or airway elastance (beta 2). Skeletal muscle is suggested as a better beta 2 adrenoceptor model than airways for use in cardioselectivity determinations.
已经开展了一项研究，以确定在体内测定β-肾上腺素能受体拮抗剂心脏选择性的最佳方法，以麻醉猫制备中的阿替洛尔为例。使用三种β-肾上腺素能受体激动剂：特布他林（β2）、多巴酚丁胺（β1）和异丙肾上腺素，并监测阿替洛尔对激动剂对心率、气道弹性和比目鱼肌张力影响的拮抗作用，在每个参数上观察到每种激动剂剂量-反应曲线的平行位移。通过比较Schild图中的DR10值和平均剂量比位移，用每种激动剂测定阿替洛尔的心脏选择性。得出结论，通过比较阿替洛尔对多巴酚丁胺（β1）对心率（β1）的拮抗作用与其对特布他林（β2）对比目鱼肌张力（β2）或气道弹性（β2）的拮抗作用，能最好地确定阿替洛尔的心脏选择性。建议在心脏选择性测定中，骨骼肌比气道更适合作为β2肾上腺素能受体模型。
