Muscarinic acetylcholine receptor M1 and Muscarinic acetylcholine receptor M3 (CHRM1 (for M1), CHRM3 (for M3))

Muscarinic acetylcholine receptors M1 and M3 are two members of the five muscarinic receptor subtypes, both part of the GPCR superfamily. M1 receptors are primarily expressed in the central nervous system, where they regulate higher cognitive functions, learning, memory, and neural plasticity. M3 receptors are widely distributed in peripheral tissues, including smooth muscle, exocrine glands, and pancreatic beta cells, controlling smooth muscle contraction, glandular secretion, and insulin release. Both receptors are coupled to Gq/11 proteins, leading to activation of phospholipase C and generation of intracellular calcium signals. Dysregulation or dysfunction of these receptors is implicated in various diseases, including neurodegenerative disorders (notably Alzheimer’s disease, via M1) and metabolic and respiratory conditions (notably diabetes and asthma/COPD, via M3). While both are crucial therapeutic targets, the lack of highly subtype-selective ligands presents significant drug development and safety challenges[1][2][4][5][6][7][8].

Other names

M1 receptormAChR M1Acetylcholine receptor M1CHRM1M3 receptormAChR M3Acetylcholine receptor M3CHRM3

Agonists: Activate receptor to increase downstream signaling (Gq/11-mediated PLC activation, ↑IP₃/Ca²⁺) Antagonists: Inhibit acetylcholine binding, block receptor-mediated responses (bronchodilation, reduced gland secretion) Positive allosteric modulators: Enhance response to endogenous acetylcholine without direct activation Negative allosteric modulators: Diminish receptor activation