Cholinergics/Anticholinergics

Abstract

This article covers classes of drugs and chemicals that act directly on muscarinic and nicotinic cholinergic receptors as agonists, antagonist, or allosteric modulators, together with an overview of the structures of muscarinic and nicotinic receptors. A brief history of the use of the small molecules muscarine, nicotine, and atropine to differentiate nicotinic and muscarinic receptors both of which respond to the neurotransmitter acetylcholine. This followed by discussion of the physical nature of the muscarinic G‐protein‐coupled‐receptor and the ligand‐gated‐ion‐channel nicotinic receptor. The structure–activity relationships of muscarinic agonists and antagonists are discussed with reference to attempts to develop of drugs selective for one of the five muscarinic receptors. Muscarinic antagonists are employed to treat disease states such as asthma, COPD, and overactive bladder. Muscarinic agonists have potential in the treatment of Alzheimer's disease. The structure–activity relationships of agonists and antagonists of nicotinic receptors are presented. Nicotinic agonists have been employed to assist in smoking cessation and have potential in treating Alzheimer's disease. Nicotinic antagonists have primarily been employed as neuromuscular blockers in surgery. The use of both positive and negative allosteric modulators of both muscarinic and nicotinic are discussed.