3 α7 Nicotinic Acetylcholine Receptor Agonists and Positive Allosteric Modulators

Abstract

Publisher Summary The nicotinic acetylcholine receptors (nAChRs) are a family of cationic ligand–gated ion channels and are members of the cys-loop receptor superfamily. The α7 receptor has attracted attention as a therapeutic target for a number of disorders including schizophrenia, Alzheimer's disease, and inflammation. The chapter discusses the progress in medicinal chemistry of recent α7 nAChR agonists and the advances in the discovery of α7 nAChR positive allosteric modulators. The chapter discusses α7 nAChR positive allosteric modulators. An alternative approach to activating the receptor with an exogenous agonist is the use of a positive allosteric modulator to enhance receptor function elicited by the endogenous ligand without directly activating or desensitizing the receptor. There are several positive allosteric modulators that range from proteins to small molecules, serum albumins, ivermectin, galantamine, 5-hydroxyindole, indole derivatives, sulphonamides, aminothiazoles, enaminones, thiophene amides, and ureas. There are differences in the profiles of positive allosteric modulation of the a7 nAChR, thus, there appear to be at least 2 different mechanisms of action for positive allosteric modulation: type I and type II. But, there is a considerable scope to differentiate this compound class from agonists in animal models, and ultimately in the clinic, with potential benefit to patients suffering from a number of debilitating neuropsychiatric, neurological, and inflammatory disorders.