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

Muscarinic acetylcholine receptors M1–M5 collectively represent a subfamily of G protein-coupled receptors (GPCRs) that mediate the actions of acetylcholine throughout the central and peripheral nervous system[6][4][2][1][5]. The five subtypes (M1, M2, M3, M4, M5) show differing tissue distribution and G protein coupling: M1, M3, and M5 preferentially couple to Gq/11 proteins and stimulate excitatory second messenger cascades, while M2 and M4 couple to Gi/o proteins and mediate inhibitory signaling[6][4][2]. These receptors regulate a wide range of physiological processes, including cognitive function, heart rate, smooth muscle tone, and glandular secretion, and are centrally involved in multiple diseases such as Alzheimer’s, schizophrenia, and cardiovascular disorders[5][6][2][3]. Selective pharmacological modulation is challenging due to the high conservation of the acetylcholine-binding (orthosteric) site, driving ongoing research into drugs that target allosteric binding sites specific to each subtype[1][5][2]. Many clinically used drugs are non-selective antagonists, and new compounds targeting specific subtypes (especially M1 and M4 for neuropsychiatric indications) are under investigation[1][2][5].

Other names

Muscarinic acetylcholine receptor familyMuscarinic receptor M1–M5mAChR M1–M5Cholinergic receptor, muscarinic type (M1, M2, M3, M4, M5 subtypes)

Orthosteric agonism/antagonism (at acetylcholine binding site), Allosteric modulation (at distinct non-orthosteric sites), Gq-protein signaling stimulation (M1, M3, M5), Gi/o-protein signaling inhibition (M2, M4), Inverse agonism