Effects of 2 alpha-DHET and its optical isomers on muscarinic and nicotinic receptors.

The agent 2 alpha-(2', 2'-disubstituted-2'-hydroxy-ethoxy) tropane (2 alpha-DHET), its optical isomers and atropine were compared in their ability to inhibit specific [3H]QNB binding to muscarinic receptors of guinea pig ileum and to antagonize oxotremorine- and nicotine-induced contractions of isolated guinea pig ileum. A good correlation was observed between the affinities to muscarinic receptors and the antimuscarinic potencies in isolated guinea pig ileum. The binding data for 2 alpha-DHET and its isomers were also consistent with their central and peripheral pharmacological activity in vivo. Compounds with 2'R configuration are more suitable to the stereostructure of the binding sites of muscarinic receptors than that of 2'S configuration.