Muscarinic acetylcholine receptor M1, M2, M4, M5 (mAChR M1, M2, M4, M5)

The muscarinic acetylcholine receptors M1, M2, M4, and M5 are a subset of the G protein-coupled receptor (GPCR) family that mediate the metabotropic actions of the neurotransmitter acetylcholine in the central and peripheral nervous systems (UniProt, NIH). These receptors are categorized into two groups based on their G-protein coupling: M1 and M5 are Gq-coupled (excitatory), while M2 and M4 are Gi-coupled (inhibitory) (Wikipedia, ResearchGate). In the brain, M1 and M4 receptors are highly expressed in regions like the cortex and striatum, where they play critical roles in cognitive processes, memory, and the regulation of dopaminergic signaling (BMS, NIH). M2 receptors are widely distributed and involved in heart rate regulation and presynaptic inhibition, while M5 receptors are primarily localized in the midbrain and linked to the reward and addiction pathways (StatPearls, MDPI). This specific subset is a major focus of drug development for neuropsychiatric disorders, particularly schizophrenia and Alzheimer's disease, where agonists like xanomeline aim to improve symptoms by targeting M1 and M4 while avoiding the M3-mediated peripheral side effects such as gastrointestinal distress (Wikipedia, PatSnap). Therapeutic strategies include orthosteric agonists, antagonists, and increasingly, subtype-selective positive allosteric modulators (PAMs) to achieve better precision and safety (Nature Reviews Drug Discovery, MDPI).

Other names

Muscarinic receptorsCHRM1CHRM2CHRM4CHRM5mAChRsCholinergic receptors muscarinic

Agonism, antagonism, and allosteric modulation of specific muscarinic receptor subtypes to regulate neurotransmission, cognitive function, and autonomic activity.