Glutamate ionotropic receptor (iGluR)

Glutamate ionotropic receptors (iGluRs) are tetrameric ligand-gated ion channels present throughout the nervous system, responsible for the majority of fast excitatory neurotransmission. They are activated by glutamate and sub-divided into AMPA, NMDA, kainate, and delta classes based on their pharmacology and sequence similarities. Each receptor subunit contains modular domains: the extracellular amino-terminal domain (ATD), the ligand-binding domain (LBD), the transmembrane ion channel-forming domain (TMD), and the intracellular carboxy-terminal domain (CTD). iGluRs mediate synaptic signaling and plasticity, which is crucial for learning and memory. Genetic and pharmacological evidence implicates iGluRs in a wide range of CNS diseases. Drugs targeting iGluRs are in clinical use for neurological and psychiatric disorders, but therapeutic manipulation is limited by significant safety concerns, including neurotoxicity and cognitive side effects.

Other names

Ionotropic glutamate receptoriGluRGlutamate-gated ion channelAMPA receptor (subtype)NMDA receptor (subtype)Kainate receptor (subtype)Delta receptor (subtype)

Antagonism/inhibition (block ion channel to reduce excitatory neurotransmission); Allosteric modulation (Increase or decrease receptor function via non-competitive sites); Channel blocking (e.g., Mg(^2+) block in NMDA receptors); Positive or negative modulation (e.g., promoting or inhibiting receptor opening)