Brandt H D, Offermeier J
Arch Int Pharmacodyn Ther. 1977 Feb;225(2):180-95.
An antagonist acting on its own receptor leading to a gradual decrease in the affinity between an agonistic drug and its own but different receptor, is a metaffinoid antagonist. The presently published models for metaffinoid antagonism predict a parallel shift in the concentration-effect curves of the agonist by the metaffinoid antagonist, due to a gradual change in the affinity between the agonist and its receptor. An alternative model is proposed where the presence of an antagonist changes the affinity of only a fraction of the agonistic receptors, leading, in contrast to the presently published model to: a) non-parallel shifts in concentration-effect curves and b) metaffinoid antagonistic curves that look like the curves obtained in metactoid antagonism. Experimental support for the alternative model is found in the interaction between various beta-adrenergic agonists and serotonin in the guinea-pig tracheal chain and rat stomach fundus strip preparations.
作用于自身受体导致激动剂与其自身但不同受体之间亲和力逐渐降低的拮抗剂是类石蜡拮抗剂。目前已发表的类石蜡拮抗模型预测，由于激动剂与其受体之间亲和力的逐渐变化，类石蜡拮抗剂会使激动剂的浓度-效应曲线发生平行移动。本文提出了另一种模型，即拮抗剂的存在仅改变一部分激动受体的亲和力，与目前已发表的模型相反，这会导致：a）浓度-效应曲线的非平行移动；b）类石蜡拮抗曲线类似于在变构拮抗中获得的曲线。在豚鼠气管链和大鼠胃底条制备物中各种β-肾上腺素能激动剂与5-羟色胺之间的相互作用中发现了对该替代模型的实验支持。
