Muscarinic acetylcholine receptor M2 and other non-M3 muscarinic receptor subtypes (M2, M1, M4, M5)

The muscarinic acetylcholine receptor M2 and other non-M3 subtypes (M1, M4, and M5) are a group of G protein-coupled receptors (GPCRs) that mediate the effects of the neurotransmitter acetylcholine. These receptors are widely distributed throughout the body, with the M2 subtype being predominantly located in the heart, where it plays a vital role in slowing the heart rate via Gi protein signaling (UniProt P08172). The M1, M4, and M5 subtypes are primarily found in the central nervous system, where they regulate cognitive processes, locomotor activity, and dopamine release (IUPHAR/BPS Guide to Pharmacology). Specifically, M1 and M4 receptors are significant therapeutic targets for neuropsychiatric conditions like schizophrenia and Alzheimer's disease due to their roles in cortical and striatal signaling (PubMed PMID: 28937030). Drugs targeting these receptors include non-selective agents like atropine and subtype-preferring agents like xanomeline, which targets M1 and M4 to treat psychosis (NIH/NIMH). Therapeutic development often focuses on these non-M3 subtypes to avoid the common side effects associated with M3 receptor inhibition, such as xerostomia and constipation (StatPearls). The M2 receptor also acts as a presynaptic autoreceptor in the brain, inhibiting the further release of acetylcholine (UniProt P08172). M5 receptors, though less studied, are implicated in the reward circuitry and vascular tone in the brain (UniProt P08912).

Other names

CHRM1CHRM2CHRM4CHRM5Muscarinic acetylcholine receptor 1Muscarinic acetylcholine receptor 2Muscarinic acetylcholine receptor 4Muscarinic acetylcholine receptor 5Non-M3 muscarinic receptors

Selective or non-selective agonism or antagonism of muscarinic receptor subtypes M1, M2, M4, and M5 to modulate parasympathetic and central nervous system activity.