Muscarinic acetylcholine receptor M3-M5 (CHRM3-CHRM5) (CHRM3-5)

The human muscarinic acetylcholine receptors M3, M4, and M5 (encoded by the CHRM3, CHRM4, and CHRM5 genes) are G protein-coupled receptors (GPCRs) that mediate the physiological effects of acetylcholine in the central and peripheral nervous systems [1, 16]. M3 and M5 receptors primarily couple to Gq proteins to stimulate phospholipase C and increase intracellular calcium, whereas M4 receptors couple to Gi proteins to inhibit adenylyl cyclase and reduce cAMP levels [1, 4]. M3 is widely expressed in peripheral tissues, where it regulates smooth muscle contraction in the airways, gastrointestinal tract, and bladder, and stimulates secretion from exocrine glands [3, 11]. M4 and M5 are predominantly located in the brain; M4 is highly expressed in the striatum and regulates dopamine release, making it a key target for antipsychotic drug development (e.g., xanomeline, emraclidine) [2, 4]. M5 is involved in reward-related behaviors and the regulation of cerebral vascular tone, representing a potential target for addiction and vascular-related cognitive decline [7, 14]. Clinically, M3 antagonists like tiotropium and darifenacin are used for respiratory and urological disorders, while M4-selective modulators are emerging as promising therapies for schizophrenia [2, 9].

Other names

Muscarinic acetylcholine receptor M3Muscarinic acetylcholine receptor M4Muscarinic acetylcholine receptor M5Cholinergic receptor muscarinic 3Cholinergic receptor muscarinic 4Cholinergic receptor muscarinic 5CHRM3CHRM4CHRM5HM3HM4HM5

Competitive antagonism of acetylcholine binding to inhibit parasympathetic signaling (M3); Agonism or positive allosteric modulation to enhance cholinergic signaling (M4); Modulation of dopamine release and reward pathways (M4, M5).