pD2-, pA2- and pD2'-values of a series of compounds in a histaminic and a cholinergic system.
(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.
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011968:Receptors, Histamine / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D013329:Structure-Activity Relationship
D006634:Histamine H1 Antagonists; D011725:Pyridines; D011950:Receptors, Cholinergic; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1