Muscarinic acetylcholine receptor M1–M5 (mAChR M1–M5)

Muscarinic acetylcholine receptor M1–M5 refers to a family of five closely related G protein-coupled receptors (M1, M2, M3, M4, M5) that mediate most of the actions of the neurotransmitter acetylcholine in the central and peripheral nervous systems[4][1][5][6][7]. Each receptor subtype has a unique tissue distribution and G protein coupling preference (M1, M3, M5 are Gq/11-coupled, stimulating phospholipase C; M2, M4 are Gi/o-coupled, inhibiting adenylyl cyclase), leading to diverse physiological functions, from modulating cognition and motor control to regulating heart rate and smooth muscle activity[1][4][3][6]. mAChRs are major therapeutic targets in neurology, psychiatry, cardiology, pulmonology, and gastroenterology, with drugs targeting these receptors used in diseases such as Alzheimer’s disease, schizophrenia (KarXT), Parkinson’s disease, COPD, and overactive bladder[4][5]. Selective modulation of individual subtypes is an ongoing pharmacological focus in order to maximize therapeutic benefit and minimize side effects.

Other names

mAChRs M1–M5Muscarinic M1–M5 receptorsCHRM1, CHRM2, CHRM3, CHRM4, CHRM5 (gene/protein abbreviations for each subtype)Muscarinic receptor M1, Muscarinic receptor M2, etc.

Agonist (stimulates receptor signaling), Antagonist (blocks receptor signaling), Inverse agonist (reduces basal receptor activity), Allosteric modulator (modifies response to endogenous ligand; can be positive or negative)