The Muscarinic Acetylcholine Receptor M 5 : Therapeutic Implications and Allosteric Modulation

The muscarinic acetylcholine receptor (mAChR) subtype 5 (M₅) was the most recent mAChR to be cloned and has since emerged as a potential therapeutic target for a number of indications. Early studies with knockout animals have provided clues to the receptor's role in physiological processes related to Alzheimer's disease, schizophrenia, and addiction, and until recently, useful subtype-selective tools to further probe the pharmacology of M₅ have remained elusive. Small-molecule allosteric modulators have since gained traction as a means by which to selectively examine muscarinic pharmacology. This review highlights the discovery and optimization of M₅ positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs).