Muscarinic acetylcholine receptor M2-M5 (mAChR M2-M5)

The M2–M5 muscarinic receptors are a group of four G protein-coupled receptors (GPCRs) that mediate the slow, metabotropic effects of acetylcholine in the central and peripheral nervous systems [1, 9]. These receptors are functionally divided into two groups: M2 and M4, which couple to Gi/o proteins to inhibit adenylyl cyclase, and M3 and M5, which couple to Gq/11 proteins to stimulate phospholipase C and increase intracellular calcium [1, 5]. M2 receptors are critical for regulating heart rate and presynaptic inhibition, while M3 receptors are the primary mediators of smooth muscle contraction in the airways, bladder, and gastrointestinal tract, as well as glandular secretion [3, 10]. M4 and M5 receptors are predominantly expressed in the brain, where they modulate dopaminergic neurotransmission and are implicated in the pathophysiology of schizophrenia, Parkinson's disease, and drug addiction [1, 8, 15]. Clinically, these receptors are targeted by antagonists like tiotropium for COPD and oxybutynin for overactive bladder, as well as agonists like xanomeline for schizophrenia [2, 13]. A significant challenge in drug development is achieving subtype selectivity to avoid common anticholinergic side effects such as dry mouth, tachycardia, and cognitive impairment [6, 14].

Other names

CHRM2CHRM3CHRM4CHRM5Muscarinic acetylcholine receptor subtypes 2-5M2 muscarinic receptorM3 muscarinic receptorM4 muscarinic receptorM5 muscarinic receptormAChR2mAChR3mAChR4mAChR5

Agonist, Antagonist, Inverse agonist, Positive allosteric modulator (PAM)