Muscarinic acetylcholine receptor M1; Muscarinic acetylcholine receptor M3 (M1 (for M1 subtype), M3 (for M3 subtype))

Muscarinic acetylcholine receptors M1 and M3 are subtypes of a family of G protein-coupled receptors (GPCRs) activated by the neurotransmitter acetylcholine. M1 is primarily located in the CNS (cortex, hippocampus), regulating cognitive function, memory, and learning, while M3 is abundant in peripheral tissues such as smooth muscle, glands, and the pancreas, where it regulates muscle contraction, glandular secretion, and insulin release. Both receptors signal mainly through Gq proteins, leading to activation of phospholipase C, increased inositol trisphosphate (IP3) and calcium, and downstream cellular effects. These receptors are validated therapeutic targets for neuropsychiatric (especially M1) and metabolic or respiratory diseases (mainly M3). A major challenge in drug development is achieving subtype selectivity to maximize therapeutic benefit while minimizing side effects associated with activity at other muscarinic receptors. Antagonists are widely used for conditions such as asthma, COPD, and gastrointestinal disorders (mainly targeting M3), while agonists and modulators of M1 are investigational or in early clinical development for cognitive and psychiatric disorders.

Other names

M1 muscarinic receptorM1-AChRCHRM1 (gene for M1)M3 muscarinic receptorM3-AChRCHRM3 (gene for M3)cholinergic receptor M1/M3

Agonists: Bind and activate muscarinic receptors, mimicking acetylcholine; increase intracellular calcium and PKC via Gq activation (M1, M3); Antagonists: Block acetylcholine action at muscarinic receptors, reducing receptor-mediated signaling; Allosteric modulators: Bind to sites distinct from acetylcholine-binding pocket, modulating receptor activity