Cholinergic receptor muscarinic 3 and 5 (CHRM3 and CHRM5) (CHRM3/CHRM5)

Cholinergic receptor muscarinic 3 (CHRM3) and 5 (CHRM5) are G protein-coupled receptors (GPCRs) that play a pivotal role in the vestibular system, which governs balance and spatial orientation. These receptors are expressed in the vestibular nuclei of the brainstem and the hair cells of the inner ear, where they facilitate cholinergic neurotransmission (UniProt P20366, P08912). In vestibular disorders such as motion sickness and Meniere's disease, excessive cholinergic signaling in these pathways leads to symptoms like vertigo, nausea, and vomiting (StatPearls: Motion Sickness). Drugs targeting these receptors, most notably scopolamine, act as antagonists to reduce the sensitivity of the vestibular apparatus to motion stimuli (PubMed: 11579133). While CHRM3 is also heavily involved in smooth muscle contraction and glandular secretion, its specific function in the vestibular nuclei makes it a key target for anti-emetic therapy. CHRM5 receptors, though less characterized, are believed to modulate dopamine release and contribute to the integration of sensory inputs within the vestibular complex (PubMed: 25814045). This dual-receptor involvement in the vestibular pathway highlights the complexity of balance regulation and the therapeutic potential of subtype-specific muscarinic modulation.

Other names

CHRM3CHRM5M3RM5RCholinergic receptor muscarinic 3Cholinergic receptor muscarinic 5Muscarinic acetylcholine receptor M3Muscarinic acetylcholine receptor M5

Competitive antagonism of muscarinic acetylcholine receptors (specifically M3 and M5 subtypes) in the vestibular nuclei and the vomiting center, which inhibits the transmission of excitatory signals from the inner ear to the brain, thereby reducing motion-induced nausea and vertigo (StatPearls: Motion Sickness; PubMed: 11579133).