Muscarinic acetylcholine receptor M1 and M3 (M1/M3 mAChR)

Muscarinic acetylcholine receptors M1 and M3 are G protein-coupled receptors (GPCRs) that mediate the physiological responses to acetylcholine in the central and peripheral nervous systems (UniProt: P11229, P20366). The M1 receptor is primarily expressed in the cerebral cortex, hippocampus, and autonomic ganglia, playing a vital role in cognitive functions and ganglionic transmission (PubMed: 25221970). The M3 receptor is found on smooth muscle cells, particularly in the airways and bladder, as well as in exocrine glands, where it triggers contraction and secretion (StatPearls: Physiology, Cholinergic Receptors). In therapeutic applications for respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD), drugs are engineered to target both receptors but exhibit a kinetic preference for M3, characterized by a significantly slower dissociation rate compared to M2 or M1 (PubChem: Tiotropium). This kinetic selectivity ensures prolonged bronchodilation and reduces the need for frequent dosing, which is a hallmark of Long-Acting Muscarinic Antagonists (LAMAs) (PubMed: 16226540). Despite their therapeutic utility, the broad distribution of these receptors leads to common anticholinergic side effects, including dry mouth, urinary retention, and potential cognitive effects if the drugs cross the blood-brain barrier (NIH: LiverTox, Anticholinergic Drugs).

Other names

CHRM1CHRM3Cholinergic receptor muscarinic 1Cholinergic receptor muscarinic 3M1 muscarinic receptorM3 muscarinic receptor

Competitive antagonism of acetylcholine at M1 and M3 receptors, with a specific kinetic profile favoring long-residency time at the M3 subtype to inhibit bronchoconstriction.