M2 muscarinic acetylcholine receptor; M3 muscarinic acetylcholine receptor (M2 receptor (M2R); M3 receptor (M3R))

The **M2 muscarinic acetylcholine receptor** (M2R) and **M3 muscarinic acetylcholine receptor** (M3R) are two subtypes of the muscarinic acetylcholine receptor family, which belong to the broader class of G protein-coupled receptors (GPCRs)[1][4][10]. These receptors are activated by the neurotransmitter acetylcholine and mediate many of the parasympathetic responses in the body. M2R is primarily expressed in the heart, where it functions to slow cardiac pacemaking and reduce heart contractility via Gi protein-mediated inhibition of adenylyl cyclase[10]. M3R is predominantly expressed in smooth muscle (such as lungs, vasculature, and bladder) and glandular tissues, mediating contraction (bronchoconstriction, bladder voiding) and stimulating secretions through Gq-mediated activation of phospholipase C and increased intracellular calcium[4][10]. Both receptors are clinically significant drug targets: M2R for its role in heart rate modulation and M3R for its regulation of smooth muscle tone, especially in diseases such as COPD, overactive bladder, and asthma[2][3][8]. Therapies frequently aim to block M3R-mediated bronchoconstriction with inhaled antimuscarinic drugs while minimizing undesired cardiovascular effects from the blockade of M2R; thus, selectivity and careful dosing are major therapeutic challenges[2][8]. Both receptors are implicated in additional pathologies, including cancer and some CNS diseases[5][6]. Structural studies of these receptors have facilitated the rational design of more selective drugs and the identification of novel allosteric modulators[1][2][7].

Other names

M2 receptorM3 receptorM2RM3Rmuscarinic acetylcholine receptor M2muscarinic acetylcholine receptor M3CHRM2CHRM3mAChR M2mAChR M3

Antagonism (blockade of acetylcholine binding, e.g., in bronchoconstriction and overactive bladder); Agonism (activation of receptor—less common clinically, primarily as research tools and in some CNS disorders); Allosteric modulation (targeting sites outside the acetylcholine-binding pocket, for improved selectivity); Inverse agonism (for experimental compounds)