Doggrell S A
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
Chirality. 1993;5(1):8-14. doi: 10.1002/chir.530050103.
The effects of (+/-)-, (+)-, and (-)-atenolol, sotalol, and amosulalol alone on the rat left atria and portal vein and on the respective beta 1- and beta 2-adrenoceptor-mediated responses to isoprenaline have been determined. (+/-)-Atenolol at 10(-6) M had no effect whereas high concentrations of (+/-)- and (-)-sotalol, 10(-5)-10(-4) M, and (+/-)-, and (-)-amosulalol depressed the response of the rat left atria to cardiac stimulation which indicates membrane stabilizing activity. None of the drugs tested had any effect alone on the rat portal vein. The order of potency as antagonists was (+/-)-amosulalol > (+/-)-atenolol > (+/-)-sotalol at beta 1-adrenoceptors and (+/-)-amosulalol > (+/-)-sotalol > (+/-)-atenolol at beta 2-adrenoceptors. (+/-)-Atenolol and (+/-)-amosulalol are beta 1-selective whereas (+/-)-sotalol is beta 2-selective. For each of the racemic beta-blockers, the beta 1- and beta 2-adrenoceptor blocking activity was predominantly due to the (-)-enantiomer.
已测定了（±）-、（+）-和（-）-阿替洛尔、索他洛尔和阿默洛尔单独对大鼠左心房和门静脉以及对异丙肾上腺素各自β1和β2肾上腺素能受体介导反应的影响。10^(-6) M的（±）-阿替洛尔无作用，而高浓度（10^(-5)-10^(-4) M）的（±）-和（-）-索他洛尔以及（±）-和（-）-阿默洛尔抑制大鼠左心房对心脏刺激的反应，这表明其具有膜稳定活性。所测试的药物单独对大鼠门静脉均无任何作用。作为拮抗剂的效力顺序在β1肾上腺素能受体处为（±）-阿默洛尔＞（±）-阿替洛尔＞（±）-索他洛尔，在β2肾上腺素能受体处为（±）-阿默洛尔＞（±）-索他洛尔＞（±）-阿替洛尔。（±）-阿替洛尔和（±）-阿默洛尔是β1选择性的，而（±）-索他洛尔是β2选择性的。对于每种消旋β受体阻滞剂，β1和β2肾上腺素能受体阻断活性主要归因于（-）-对映体。
