title: Quantitative correlations between chemical structure and affinity for acetylcholine receptors.
abstract: The affinity constants (log K, pA2) of 128 quaternary ammonium compounds belonging to several different series have been correlated linearly with the hydrophobicity (piR) constant, the dipole moment (muR), and the number of hydroxyl groups (nOH) of the side chain; the dependence on the hydrophobicity constant of the quaternary ammonium head (pi-N identical to) is shown to be parabolic. A correlation coefficient of 0.96 is obtained for all the compounds using only 4 independent variables (6 terms). Based on the quantitative correlation obtained, intermolecular forces involved in the drug-receptor interaction are discussed. Further molecular modifications to enhance the affinity to cholinergic receptors are suggested.
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008433:Mathematics; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds / Q000378:metabolism* / Q000494:pharmacology; D011950:Receptors, Cholinergic; D012044:Regression Analysis; D013329:Structure-Activity Relationship
chemical_list: D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds; D011950:Receptors, Cholinergic; D000109:Acetylcholine