Muscarinic acetylcholine receptors M1–M3 (mAChR M1–M3)

Muscarinic acetylcholine receptors M1, M2, and M3 are a subgroup of G protein-coupled receptors that mediate the physiological effects of the neurotransmitter acetylcholine across the central and peripheral nervous systems [5, 14]. The M1 and M3 subtypes primarily couple to Gq proteins, activating the phospholipase C pathway to increase intracellular calcium, which is essential for cognitive processes, glandular secretions, and smooth muscle contraction [1, 8, 18]. In contrast, the M2 subtype couples to Gi proteins to inhibit adenylyl cyclase, playing a vital role in regulating heart rate and modulating neurotransmitter release [5, 17]. These receptors are key therapeutic targets for conditions such as Alzheimer's disease, chronic obstructive pulmonary disease (COPD), and overactive bladder [2, 7, 9]. Clinical management involves the use of agonists like pilocarpine to treat glaucoma and antagonists like tiotropium for respiratory relief [12, 14]. However, the high structural similarity between these subtypes often leads to off-target effects, such as dry mouth and tachycardia, presenting a significant challenge in drug development [14, 16].

Other names

CHRM1CHRM2CHRM3M1 receptorM2 receptorM3 receptorMuscarinic acetylcholine receptor subtypes 1-3mAChR M1-M3

Muscarinic acetylcholine receptors M1, M2, and M3 are targeted by agonists and antagonists to modulate parasympathetic activity. Agonists (e.g., pilocarpine) stimulate these receptors to increase secretions and smooth muscle tone, while antagonists (e.g., atropine, tiotropium) block acetylcholine binding to reduce secretions, relax smooth muscle, or increase heart rate [5, 14]. M1 and M3 primarily couple to Gq proteins to activate phospholipase C, while M2 couples to Gi to inhibit adenylyl cyclase [14, 19].