Freeman K A, Tallarida R J
Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
J Pharmacol Methods. 1991 Mar;25(1):11-8. doi: 10.1016/0160-5402(91)90018-z.
A formula derived by Gero and Tallarida (1977) relates the equilibrium dissociation constant of a partial agonist (P) and that of a second agonist (A) of greater efficacy that acts on the same receptor. The second agonist may or may not be a strong agonist. Accordingly, if the dissociation constant (K) of one of the compounds is known, say from the method of partial irreversible receptor blockade, then the dissociation constant for the other may be determined from the complete concentration-effect curves of the compounds and the derived formula: kp = KA (Ap-Ai)Pi/(Ap + KA)Ai, where Pi and Ai are equieffective concentrations of P and A, Ap = the concentration of A that gives an effect = the maximum effect of P. The practical use of this formula is illustrated here for several agonists, and for each, the value of K obtained is compared to that obtained by partial irreversible receptor blockade. In all cases tested, the agreement is quite good, thus suggesting that this method may be a practical alternative.
杰罗和塔拉里达（1977年）推导的一个公式，涉及作用于同一受体的部分激动剂（P）的平衡解离常数和效力更强的第二种激动剂（A）的平衡解离常数。第二种激动剂可能是强效激动剂，也可能不是。因此，如果其中一种化合物的解离常数（K）已知，比如通过部分不可逆受体阻断法得知，那么另一种化合物的解离常数可根据这些化合物的完整浓度-效应曲线以及推导公式来确定：kp = KA (Ap - Ai)Pi/(Ap + KA)Ai，其中Pi和Ai分别是P和A的等效浓度，Ap = 产生与P的最大效应相同效应的A的浓度。本文针对几种激动剂说明了该公式的实际应用，并将每种激动剂通过该公式得到的K值与通过部分不可逆受体阻断法得到的K值进行了比较。在所有测试案例中，二者吻合度相当高，这表明该方法可能是一种切实可行的替代方法。
