Effect of Deoxamuscarine Etherification on M2 and M3 Muscarinic Affinity and Efficacy

A series of ether derivatives of deoxamuscarine were synthesized and tested for muscarinic activity on guinea-pig heart, ileum, and bladder. The results show that: a) The introduction ofthe benzyl group generates an agonist which is 5-fold more potent and 10-fold more selective than deoxamuscarine on ileum. This selectivity is ascribed to an increase of efficacy. b) Affinity and efficacy are differently affected by the substituents studied. c) The so-called muscarinic subsite interacting with the hydroxy group of muscarine-like compounds may acconìmodate bulky substituents, and on the basis of this new functionalized congeners may be designed with a view to achieving more potent and more selective muscarinic ligands.