Structural Parameters Determining Cholinergic and Anticholinergic Activities in a Series of 1, 3-Dioxolanes

A series of 1,3-dioxolane-4-dimethylaminomethyl methiodides substituted at the 2 position with alkyl and aryl groups have been examined for their agonist and antagonist activities at muscarinic receptors in guinea pig ileal muscle and rat jejunum. Complete lack of stereoselectivity of antagonist activity was found with the enantiomers of the 2,2-diphenyl and the 2-phenyl-2-cyclohexyl derivatives. A reasonable correlation of pA2 and π was observed. pA2 values appeared independent of the agonist employed. Selected compounds were examined for their antihistaminic activities: these were 100-500 times less than the anticholinergic activities but were similarly nonstereoselective.