NR2Cselective

NR2Cselective refers to compounds or ligands that preferentially modulate NMDA receptors containing the NR2C subunit (NR1/NR2C), as opposed to receptors with NR2A, NR2B, or NR2D subunits. The NMDA receptor is a heterotetramer composed of two NR1 subunits and two NR2 subunits, with NR2C being one of the possible subunits encoded by the GRIN2C gene. NR2C subunits are most prominently expressed in the cerebellum, with more limited distribution in other brain regions and notable developmental regulation.

Pharmacology and research use: NR2Cselective ligands can function as antagonists or as positive/negative allosteric modulators that show higher potency or efficacy at NR1/NR2C receptors. These ligands are typically identified and characterized using recombinant expression systems such as HEK293 cells or Xenopus oocytes, where responses are compared across NR1/NR2A, NR1/NR2B, NR1/NR2C, and NR1/NR2D receptor assemblies. Selectivity is quantified using IC50 or EC50 values and related pharmacological metrics. Achieving robust NR2C selectivity is challenging due to conserved subunit interfaces, and many reported compounds exhibit partial preference or limited in vivo activity.

Distribution, function, and potential applications: NR2C-containing receptors contribute to both synaptic and extrasynaptic NMDA signaling and display distinctive biophysical properties, including nuanced Mg2+ block and slower deactivation relative to some other subtypes. This can influence calcium signaling and neuronal excitability in cerebellar circuits and beyond. NR2Cselective agents are mainly valuable as research tools to dissect NR2C-specific signaling and may offer insights for potential therapeutic strategies in conditions where NR2C activity is implicated, though in vivo validation remains limited.

See also: NMDA receptor, GRIN2C, subunit-selective ligands.