Category: receptor_pharmacology
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels — distinct from muscarinic ACh (Gq/Gi GPCRs, [[muscarinic_receptor_subtypes]]). Three major locations: (1) Neuromuscular junction (NMJ) — exclusively α1β1δε (adult) or α1β1δγ (fetal/denervated) muscle-type pentamers; succinylcholine, rocuronium, vecuronium, pancuronium, atracurium = NMJ-targeted neuromuscular blockers. (2) Autonomic ganglia — α3β4 (with α5 modulatory subunit); ganglionic blockers (historical: hexamethonium, trimethaphan) lost favor due to side-effect breadth. (3) CNS — α4β2 (dominant high-affinity nicotine binding; addiction + cognition target — varenicline partial agonist for smoking cessation) and α7 homopentamer (rapidly desensitizing; cognitive + cholinergic anti-inflammatory pathway via spleen vagal-nicotinic axis). Receptor states: closed → open (ms) → desensitized (s–min) → closed; chronic nicotine + α4β2-selective partial agonists drive desensitization → paradoxical functional block of fast-onset activation. Biased modulators: PAMs (galantamine on α7 and some α4β2) enhance ACh response without direct agonism. Neuromuscular blockade reversal: AChEi (neostigmine, edrophonium, pyridostigmine) restore ACh competition; sugammadex sequesters rocuronium/vecuronium directly. Smoking cessation: varenicline α4β2 partial agonist (Champix/Chantix); bupropion adjunct (DA/NE reuptake + nAChR antagonist). Cross-links: [[acetylcholine_axis]] (ACh synthesis + release upstream), [[neuromuscular_junction_blockade]] (clinical use).