Nicotinic acetylcholine and ionotropic glutamate receptors (nAChR/iGluR)

Nicotinic acetylcholine receptors (nAChRs) and ionotropic glutamate receptors (iGluRs) are two distinct classes of ligand-gated ion channels that mediate fast excitatory neurotransmission in the mammalian nervous system [1, 2]. nAChRs are pentameric proteins belonging to the Cys-loop superfamily, primarily conducting sodium and calcium ions upon binding of acetylcholine or nicotine [3]. In contrast, iGluRs are tetrameric assemblies—categorized into NMDA, AMPA, and kainate subtypes—that respond to glutamate to facilitate cation influx and regulate synaptic plasticity and long-term potentiation [4]. Both receptor families are critical therapeutic targets; for instance, nAChR modulators are used in smoking cessation and Alzheimer's disease, while iGluR antagonists like memantine and ketamine are employed for dementia and treatment-resistant depression, respectively [5, 6]. Because these receptors are ubiquitous and involve complex subunit compositions, drug development often focuses on subtype-specific ligands to minimize off-target effects such as cardiovascular instability or psychotomimetic reactions [1, 7].

Other names

nAChRiGluRLigand-gated ion channelsExcitatory ionotropic receptorsCys-loop receptors (nAChR component)Glutamate-gated ion channels (iGluR component)

Agonism, partial agonism, non-competitive antagonism (channel blocking), and positive/negative allosteric modulation of cation-selective ion channels, leading to changes in membrane potential and intracellular signaling [1, 4].