Muscarinic acetylcholine receptor M1 (CHRM1) (CHRM1)

The Muscarinic acetylcholine receptor M1 (CHRM1) is a Class A G protein-coupled receptor (GPCR) predominantly expressed in the cerebral cortex, hippocampus, and striatum of the central nervous system (UniProt: P11229). It primarily signals through the Gq/11 heterotrimeric G protein, activating phospholipase C and increasing intracellular calcium levels to modulate neuronal excitability and synaptic plasticity (IUPHAR/BPS Guide to Pharmacology). This receptor is a major mediator of cholinergic signaling related to higher cognitive functions, including learning, memory, and attention (PubMed: 28934319). In neurodegenerative conditions like Alzheimer's disease, M1 receptor activation is hypothesized to reduce amyloid-beta production and tau phosphorylation, making it a high-priority therapeutic target (PubMed: 30115515). Furthermore, M1 receptors are implicated in the pathophysiology of schizophrenia, where their modulation may alleviate cognitive and positive symptoms (StatPearls: Cholinergic Receptors). Pharmacological targeting of M1 has evolved from non-selective orthosteric agonists, which often caused dose-limiting peripheral side effects (e.g., GI distress, salivation), to highly selective positive allosteric modulators (PAMs) and dual-acting agents like KarXT (Xanomeline/Trospium) (PubMed: 33536144).

Other names

Cholinergic receptor muscarinic 1M1 muscarinic receptorM1RCHRM1

Agonism of the Gq/11-coupled signaling pathway to enhance cholinergic neurotransmission; Positive allosteric modulation to increase receptor sensitivity to endogenous acetylcholine; Antagonism to block cholinergic signaling.