New advances in NMDA receptor pharmacology

Trends Pharmacol Sci. 2011 Dec;32(12):726-33. doi: 10.1016/ Epub 2011 Oct 11.


N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diversity of NMDA receptors and are distinctly expressed during development and among brain regions. Thus, subunit-selective antagonists and modulators that differentially target the GluN2 subunit might provide an opportunity to pharmacologically modify the function of select groups of neurons for therapeutic gain. A flurry of clinical, functional and chemical studies have together reinvigorated efforts to identify subunit-selective modulators of NMDA receptor function, resulting in a handful of new compounds that appear to act at novel sites. Here, we review the properties of new emerging classes of subunit-selective NMDA receptor modulators, which we predict will mark the beginning of a productive period of progress for NMDA receptor pharmacology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Allosteric Regulation / drug effects
  • Animals
  • Binding Sites
  • Humans
  • Ligands
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / metabolism
  • Membrane Transport Modulators / pharmacology*
  • Membrane Transport Modulators / therapeutic use
  • Protein Conformation
  • Protein Isoforms / agonists
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Subunits / agonists
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Receptors, N-Methyl-D-Aspartate / agonists*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / chemistry
  • Receptors, N-Methyl-D-Aspartate / metabolism


  • Ligands
  • Membrane Transport Modulators
  • Protein Isoforms
  • Protein Subunits
  • Receptors, N-Methyl-D-Aspartate