Muscarinic acetylcholine receptor M2 (CHRM2) and M3 (CHRM3) (mAChR M2/M3)

Muscarinic acetylcholine receptors M2 and M3 are G protein-coupled receptors (GPCRs) that play pivotal roles in the parasympathetic nervous system by responding to the neurotransmitter acetylcholine. The M2 receptor (CHRM2) is primarily coupled to Gi proteins and is highly expressed in the heart, where it mediates bradycardia, and in the central nervous system, where it acts as an autoreceptor to inhibit further acetylcholine release (UniProt P08172). The M3 receptor (CHRM3) is coupled to Gq proteins and is found in exocrine glands and smooth muscles of the gastrointestinal tract, bladder, and airways, where it triggers secretion and contraction (UniProt P20366). These receptors are major therapeutic targets for conditions such as overactive bladder (OAB) and chronic obstructive pulmonary disease (COPD), where M3 antagonists are used to reduce muscle spasms and bronchoconstriction. However, achieving high selectivity is challenging; for instance, M3-targeted drugs for OAB often interact with M2 receptors, potentially causing cardiovascular side effects like tachycardia (PubMed: 15113735). Additionally, systemic antagonism of these receptors is associated with classic anticholinergic effects, including dry mouth, blurred vision, and constipation. Understanding the functional bias and subtype selectivity between M2 and M3 is crucial for developing more effective treatments with reduced side-effect profiles.

Other names

CHRM2CHRM3Muscarinic receptor 2Muscarinic receptor 3Cholinergic receptor muscarinic 2Cholinergic receptor muscarinic 3

Drugs targeting these receptors typically act as competitive antagonists to inhibit parasympathetic overactivity in the bladder or lungs, or as agonists to stimulate glandular secretion and ocular drainage (IUPHAR/BPS Guide to Pharmacology).