Mutschler_1983_Arzneimittelforschung_33_806

In the course of investigations of structure and conformation-activity relationships of heterocyclic acetylcholine analogues, the tertiary and quaternary methyl esters of arecaidine and the methyl ester of sulfoarecaidine were tested for their cholinergic activities. The conformational behaviour and the electronic structures of these cholinergics were investigated by quantum chemical calculations using Extended Huckel Theory (EHT) and Complete Neglect of Differential Overlap (CNDO/2)methods. The results show that the muscarinic potency of the heterocyclic analogues is dependent on structure and conformational behaviour of the onium center. The divergent charge distribution around the cationic heads of the ammonium and sulfonium derivatives, respectively, as well as differences in the dimensions of the two heterocyclic systems, can not be utilized to explain the differences in muscarinic potency of the arecaidine and sulfoarecaidine methyl esters.