Muscarinic acetylcholine receptor M2 & M3 (M2 and M3)

Muscarinic acetylcholine receptor M2 and M3 are two subtypes of muscarinic receptors, members of the G protein-coupled receptor (GPCR) superfamily, activated by the neurotransmitter acetylcholine. M2 is predominantly found in cardiac tissue, where it mediates inhibitory parasympathetic regulation of heart rate and contractility via Gi protein coupling. M3 is chiefly expressed in smooth muscle and glandular tissues, where it mediates excitatory responses—including smooth muscle contraction and glandular secretion—through Gq protein coupling. Both receptors are critical to autonomic nervous system function and have long-standing roles as drug targets in cardiovascular, respiratory, and neuropsychiatric diseases. Although highly homologous, selective targeting of M2 versus M3 subtypes is a major challenge and an ongoing objective in drug development due to overlapping binding pockets and physiological functions[1][2][3][4][5][7][9].

Other names

CHRM2Muscarinic receptor M2M2 muscarinic receptorCardiac muscarinic receptorCHRM3Muscarinic receptor M3M3 muscarinic receptorGlandular muscarinic receptor

Orthosteric antagonists: competitively inhibit acetylcholine binding - Allosteric modulators: modulate receptor response by binding at non-orthosteric sites - Bitopic ligands: bridge both orthosteric and allosteric sites, promising for selectivity[2][3] - Agonists: mimic acetylcholine to induce receptor activation