An alternative model for non-competitive antagonism.
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.
D000818:Animals; D001667:Binding, Competitive; D004336:Drug Antagonism; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009921:Metaproterenol / Q000494:pharmacology; D008954:Models, Biological; D008968:Molecular Conformation; D011955:Receptors, Drug / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D013578:Synephrine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D011955:Receptors, Drug; D012701:Serotonin; D009921:Metaproterenol; D007545:Isoproterenol; D013578:Synephrine