Quantitative Correlations and Reexamination of the Importance of Hydrophobic and Steric Factors in Anticholinergic Drug Receptor Interactions

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Abstract
The pA2 (or log K) values at the muscarinic cholinergic receptor of the guinea pig ileum for a series of 1,3-dioxolanes have been correlated with the hydrophobic constant π and π2. A correlation coefficient of 0.97 and standard deviation of 0.30 were obtained with 16 of the 18 compounds (P < 0.05). A series of 17 analogues of amino esters of α-methyl tropic acid and α-substituted phenyl acetic acids, which were tested in the isolated rat ileal muscle, was analyzed, with a correlation coefficient of 0.92 and a standard deviation of 0.25 (P < 0.05). Based on these results, the role of hydrophobic forces in the drug receptor interactions of muscarinic cholinergic receptors was analyzed. Optimum values for the physicochemical parameters were determined and their use in enhancing potency was suggested.