1 Stereochemical Aspects of Parasympathomimetics and their Antagonists: Recent Developments

Abstract

This chapter discusses recent development in the stereochemical aspects of acetylcholine (ACh) and its congeners and antagonists. During the past few years, much effort has been made to define the pharmacophoric or active conformation of cholinergic molecules in the search for clues about the molecular nature of cholinergic receptors and the ways in which their agonists and antagonists combine with the receptors. The chapter discusses questions on (1) the “active” conformation of a cholinergic ligand, (2) the existence of a unique mode of ligand binding to cholinergic receptors or the existence of multiple modes, (3) the dual effects of ACh and their explanation in terms of conformational isomerism, and (4) the binding sites that the agonist and antagonist ligands occupy. In compounds with cholinergic properties, whether muscarinic or nicotinic, it is desirable that as much evidence as possible be gathered about their mode of action since meaningful structure-activity relationships may only be derived from a group of agents when it is established that they produce their pharmacological effects through interaction at a common receptor system.