Muscarinic acetylcholine receptor M1 (CHRM1) and Muscarinic acetylcholine receptor M2 (CHRM2) (CHRM1/CHRM2)

Muscarinic acetylcholine receptors M1 and M2 are integral membrane proteins belonging to the Class A G protein-coupled receptor (GPCR) family that mediate the metabotropic actions of acetylcholine. The M1 receptor is primarily localized in the central nervous system, specifically the cerebral cortex and hippocampus, where it couples to Gq/11 proteins to facilitate cognitive processes such as learning and memory (UniProt P11229). In contrast, the M2 receptor is predominantly expressed in cardiac tissue and the hindbrain, coupling to Gi/o proteins to inhibit adenylate cyclase and regulate heart rate via vagal stimulation (UniProt P08172). These receptors are critical therapeutic targets; M1 agonists and positive allosteric modulators are extensively researched for treating cognitive deficits in Alzheimer's disease and Schizophrenia (PubMed PMID: 28802117). M2 receptors are targeted for cardiovascular regulation and are involved in the mechanism of various anticholinergic drugs used in respiratory and urological conditions (StatPearls). Achieving subtype selectivity remains a significant challenge in drug development, as non-selective antagonism often leads to adverse effects like xerostomia, tachycardia, and cognitive impairment (PubChem).

Other names

M1 receptorM2 receptorCholinergic receptor muscarinic 1Cholinergic receptor muscarinic 2Muscarinic acetylcholine receptor M1Muscarinic acetylcholine receptor M2

Agonism or antagonism of G protein-coupled signaling pathways; M1 typically couples to Gq/11 to activate phospholipase C and increase intracellular calcium, while M2 couples to Gi/o to inhibit adenylate cyclase and modulate potassium channels.