Muscarinic acetylcholine receptor subtype M1 (M1)

Muscarinic acetylcholine receptors are a family of five G protein-coupled receptor subtypes (M1–M5) found in central and peripheral tissues. All are activated by acetylcholine and mediate a variety of physiological responses through coupling to G proteins (M1, M3, M5: Gq; M2, M4: Gi), impacting neurotransmission, muscle contraction/relaxation, glandular secretion, and cognitive and cardiac functions. Each subtype displays unique tissue distributions and physiological roles. Their high conservation in orthosteric binding sites presents drug development challenges; thus, current research is focused on allosteric site targeting for improved selectivity and safety. These receptors are widely studied in pharmacology for their crucial roles in both normal function and disease pathophysiology across nervous, cardiovascular, and respiratory systems.

Other names

mAChR (Muscarinic acetylcholine receptor)Chrm1, Chrm2, Chrm3, Chrm4, Chrm5 (gene symbols)M1, M2, M3, M4, M5

Orthosteric antagonism/agonism (direct acetylcholine competition). Allosteric modulation (targeting non-conserved receptor sites to alter function or drug selectivity). Gq-mediated stimulation (M1, M3, M5: lead to increased phospholipase C activity, DAG/IP3, intracellular calcium rise). Gi-mediated inhibition (M2, M4: inhibit adenylyl cyclase, decrease cAMP, decrease PKA activity).