Amidon G L, Buckner C K
J Pharmacol Exp Ther. 1981 Feb;216(2):352-6.
A dynamic approach to evaluating reversible competitive antagonists has been used in estimating the dissociation constant (apparent KB) for (+/-)-sotalol at beta adrenergic receptors which mediate a positive chronotropic response in rat atria. Cumulative dose-response curves to the beta agonists (-)-isoproterenol and (-)-soterenol were obtained after mixing each agonist with (+/-)-sotalol at fixed ratios (Q = [antagonist]/[agonist]). Experimental and theoretical dose-response curves obtained with the dynamic approach were in good agreement and the lowered maximum responses to the agonist-antagonist mixtures were dependent on Q. Also, apparent KB values for (+/-)-sotalol determined by three methods were independent of Q and agonist employed in the experiment. Apparent KB values for (+/-)-sotalol obtained by the dynamic method (6 x 10(-7)-2 x 10(-6) M) were similar to those obtained by the traditional equilibrium or static approach. As judged by the similarity of the apparent KB values derived by the two independent theoretical models, the dynamic approach may be considered an effective and alternative means to evaluate reversible competitive antagonists.
一种评估可逆竞争性拮抗剂的动态方法已被用于估算（±）-索他洛尔在β肾上腺素能受体上的解离常数（表观KB），该受体介导大鼠心房的正性变时反应。在将每种激动剂与（±）-索他洛尔以固定比例（Q = [拮抗剂]/[激动剂]）混合后，获得了对β激动剂（-）-异丙肾上腺素和（-）-索特诺醇的累积剂量-反应曲线。用动态方法获得的实验和理论剂量-反应曲线吻合良好，对激动剂-拮抗剂混合物降低的最大反应取决于Q。此外，通过三种方法测定的（±）-索他洛尔的表观KB值与实验中使用的Q和激动剂无关。通过动态方法获得的（±）-索他洛尔的表观KB值（6×10^(-7)-2×10^(-6) M）与通过传统平衡或静态方法获得的值相似。根据由两个独立理论模型得出的表观KB值的相似性判断，动态方法可被视为评估可逆竞争性拮抗剂的一种有效且替代的手段。
