Structural basis of NR2B-selective antagonist recognition by N-methyl-D-aspartate receptors. Mol Pharmacol. 2009; 75:60–74. [PubMed: 18923063

N-Methyl-D-aspartate receptors (NMDARs) are ionotropic glu-tamate receptors endowed with unique pharmacological and functional properties. In particular, their high permeability to cal-cium ions confers on NMDARs a central role in triggering long term changes in synaptic strength. Under excitotoxic pathological conditions, such as those occurring during brain trauma, stroke, or Parkinson’s or Huntington’s diseases, calcium influx through NMDAR channels can also lead to neuronal injury. This argues for the use of NMDAR antagonists as potential therapeutic agents. To date, the most promising NMDAR antagonists are ifenprodil and derivatives, compounds that act as noncompetitive inhibitors se-lective for NMDARs containing the NR2B subunit. Recent studies have identified the large N-terminal domain (NTD) of NR2B as the region controlling ifenprodil sensitivity of NMDARs. We presen