N-methyl-D-aspartate receptor and other central ligand-gated ion channels (NMDAR and other cLGICs)

This entry refers to a broad class of transmembrane proteins that function as gated pores, opening to allow the passage of ions such as Na+, K+, Ca2+, or Cl- in response to the binding of specific neurotransmitters. The N-methyl-D-aspartate (NMDA) receptor is a prominent member of the ionotropic glutamate receptor family, essential for synaptic plasticity, learning, and memory through its mediation of excitatory signals and calcium influx (Paoletti et al., 2013, Nature Reviews Neuroscience). Other central ligand-gated ion channels (cLGICs) include GABA_A receptors, which provide the primary inhibitory tone in the brain, as well as nicotinic acetylcholine, glycine, and 5-HT3 receptors (Alexander et al., 2021, British Journal of Pharmacology). These channels are fundamental to rapid signal transduction across the central nervous system and are implicated in numerous pathologies, including Alzheimer's disease, epilepsy, schizophrenia, and chronic pain (Traynelis et al., 2010, Pharmacological Reviews). Pharmacological modulation of these targets is a cornerstone of neurology and psychiatry, utilizing agonists, antagonists, and allosteric modulators to correct imbalances in neural excitability. However, because of their widespread distribution and critical physiological roles, drugs targeting these channels often carry significant risks of side effects such as sedation, cognitive disruption, or dissociative effects.

Other names

Ionotropic receptorsLigand-gated ion channelsLGICsNeurotransmitter-gated ion channelsCys-loop receptorsIonotropic glutamate receptors

Pore blocking, positive allosteric modulation, negative allosteric modulation, competitive antagonism, and agonism.