Cholinergic receptor muscarinic 1 (CHRM1) and Cholinergic receptor muscarinic 3 (CHRM3) (M1/M3 mAChR)

Muscarinic acetylcholine receptors M1 (CHRM1) and M3 (CHRM3) are essential G protein-coupled receptors (GPCRs) that mediate the effects of the neurotransmitter acetylcholine in the central and peripheral nervous systems (UniProt P11229, P20309). The M1 receptor is primarily localized in the cerebral cortex, hippocampus, and striatum, where it plays a pivotal role in cognitive functions such as learning, memory, and attention by activating the Gq/11 signaling pathway (PubMed 33035556). In contrast, the M3 receptor is widely expressed in smooth muscles, exocrine glands, and the vascular endothelium, regulating physiological processes like bronchoconstriction, gastric acid secretion, and bladder contraction (StatPearls NBK537071). Dysregulation of these receptors is implicated in several pathologies; M1 deficiency is associated with cognitive decline in Alzheimer's disease and Schizophrenia, while M3 overactivity contributes to the pathophysiology of chronic obstructive pulmonary disease (COPD) and overactive bladder (IUPHAR/BPS Guide to Pharmacology). Pharmacological intervention involves M1-selective agonists or positive allosteric modulators (PAMs) to enhance cognition, and M3-selective antagonists to alleviate respiratory and urological symptoms (PubMed 29108214). Modern therapeutic approaches, such as the combination of xanomeline and trospium, target these receptors to treat neuropsychiatric disorders while minimizing peripheral side effects (FDA 2024).

Other names

CHRM1CHRM3Muscarinic receptor 1Muscarinic receptor 3M1 receptorM3 receptormAChR M1mAChR M3Cholinergic receptor muscarinic 1Cholinergic receptor muscarinic 3

Activation of the Gq/11 signaling pathway leading to phospholipase C activation and increased intracellular calcium (agonism), or competitive inhibition of acetylcholine binding to prevent receptor activation (antagonism).