van den Brink F G, Lien E J
Eur J Pharmacol. 1977 Aug 1;44(3):251-70. doi: 10.1016/0014-2999(77)90072-3.
(1) Affinity and intrinsic activity values of 75 compounds for a histaminergic and a cholinergic system are presented. The quantitative correlations between the affinity values of 35 compounds and some physicochemical constants (Van der Waals volume, lipophilicity, number of hydrogen atoms on the protonated amine) are discussed. (2) Absence of systematic differences between pD2 and pA2 of partial agonists supports the assumption that these values are equivalent expressions of the same affinity. (3) The "mimetic moiety" in a number of the antihistaminic test compounds hardly contributes to their affinity. The affinity mainly depends on an interaction tendency with additional receptor areas. (4) The correlation between pA2 and pD2' of the whole series of compounds in the histaminergic system is artificial. The method only allows determination of both values if their ratio lies between certain limits. (5) The correlation between pA2 and pD2' for 16 closely related compounds in the guinea pig ileum and for nearly all compounds in the rat intestine has to be explained by an influence of the structural differences on drug transference and/or the less specific binding forces. (6) The metactoid receptors in the two systems are different structures. (7) Possible molecular modifications to maximize the separation of antihistaminic form cholinergic affinity are suggested.
(1) 给出了75种化合物对组胺能和胆碱能系统的亲和力及内在活性值。讨论了35种化合物的亲和力值与一些物理化学常数（范德华体积、亲脂性、质子化胺上的氢原子数）之间的定量相关性。(2) 部分激动剂的pD2和pA2之间不存在系统性差异，这支持了这些值是相同亲和力的等效表达这一假设。(3) 许多抗组胺测试化合物中的“模拟部分”对其亲和力贡献不大。亲和力主要取决于与其他受体区域的相互作用趋势。(4) 组胺能系统中整个系列化合物的pA2和pD2'之间的相关性是人为的。该方法仅在两者的比值处于一定限度内时才能同时测定这两个值。(5) 豚鼠回肠中16种密切相关化合物以及大鼠肠道中几乎所有化合物的pA2和pD2'之间的相关性，必须通过结构差异对药物转运和/或非特异性结合力的影响来解释。(6) 这两个系统中的类变形受体是不同的结构。(7) 提出了可能的分子修饰方法，以最大限度地分离抗组胺与胆碱能亲和力。
