Muscarinic acetylcholine receptor M1-M4 (mAChR M1-M4)

Muscarinic acetylcholine receptors (mAChRs) M1 through M4 are a family of G protein-coupled receptors (GPCRs) that mediate the metabotropic actions of acetylcholine in the central and peripheral nervous systems (Wikipedia, 2024; NIH, 2023). The M1 and M4 subtypes are highly expressed in the brain, particularly in the cortex, hippocampus, and striatum, where they play essential roles in learning, memory, and the regulation of dopaminergic signaling (BMS, 2025; Frontiers, 2022). Consequently, they are major therapeutic targets for treating cognitive impairment and psychosis in Alzheimer's disease and schizophrenia (Drug Discovery Today, 2019). In contrast, M2 receptors are primarily located in the heart and M3 receptors in smooth muscles and exocrine glands, where they regulate heart rate, muscle contraction, and glandular secretions, respectively (StatPearls, 2023). Pharmacological intervention involves a variety of agonists, antagonists, and allosteric modulators, though achieving subtype selectivity is crucial to avoid dose-limiting peripheral side effects like dry mouth, tachycardia, and gastrointestinal distress (Nature Reviews Drug Discovery, 2014). Recent clinical advances, such as the development of xanomeline-trospium (KarXT) and M4-selective positive allosteric modulators, aim to specifically target CNS pathways while minimizing off-target effects (Am J Psychiatry, 2022).

Other names

Muscarinic receptorsCHRM1CHRM2CHRM3CHRM4Cholinergic receptor muscarinic 1-4mAChR

Agonism, antagonism, and allosteric modulation of G protein-coupled signaling pathways (Gq for M1/M3 and Gi for M2/M4).