Muscarinic acetylcholine receptor M1 (CHRM1), Muscarinic acetylcholine receptor M2 (CHRM2), Muscarinic acetylcholine receptor M3 (CHRM3), Muscarinic acetylcholine receptor M4 (CHRM4) (M1, M2, M3, M4)

Muscarinic acetylcholine receptors M1–M4 are members of the G protein-coupled receptor family that mediate the effects of acetylcholine in the central and peripheral nervous systems[1][2][3][5]. Each subtype (M1, M2, M3, M4) is encoded by a distinct gene (CHRM1–CHRM4) and displays unique tissue distributions and G protein coupling profiles: M1 and M3 (and M5) couple to Gq proteins (excitatory), while M2 and M4 couple to Gi/o proteins (inhibitory)[5][6]. These receptors are critical modulators of cognitive, motor, and autonomic functions, and have emerged as therapeutic targets for conditions such as Alzheimer’s disease, schizophrenia, and movement disorders[1][2][3][4]. Traditional antimuscarinic drugs typically lack subtype specificity, but recent efforts to develop allosteric modulators seek to improve selectivity and minimize adverse effects[1][3]. Each subtype has distinct pharmacological and physiological roles, necessitating caution when using collective terms like "M1–M4" for precise drug development or biomarker studies.

Other names

Muscarinic receptor M1, M2, M3, M4Cholinergic receptor, muscarinic 1–4 (CHRM1–CHRM4)Muscarinic ACh receptor M1–M4Acetylcholine receptor M1–M4 (muscarinic)

Inverse agonism (e.g., tiotropium binds and inhibits receptor activity)[1][2][3]; Antagonism (classic antimuscarinics block ACh binding); Allosteric modulation (targeting sites distinct from the ACh orthosteric site for subtype selectivity)[1][2][3]; Agonism (activation by acetylcholine or muscarinic agonists)