In vitro and in vivo characterization of MPEP, an allosteric modulator of the metabotropic glutamate receptor subtype 5: review article

Amino Acids. 2002;23(1-3):207-11. doi: 10.1007/s00726-001-0130-6.


There is a need to identify subtype-specific ligands for mGlu receptors to elucidate the potential of these receptors for the treatment of nervous system disorders. To date, most mGlu receptor antagonists are amino acid-like compounds acting as competitive antagonists at the glutamate binding site located in the large extracellular N-terminal domain. We have characterized novel subtype-selective mGlu(5) receptor antagonists which are structurally unrelated to competitive mGlu receptor ligands. Using a series of chimeric receptors and point mutations we demonstrate that these antagonists act as inverse agonists with a novel allosteric binding site in the seven-transmembrane domain. Recent studies in animal models implicate mGlu(5) receptors as a potentially important therapeutic target particularly for the treatment of pain and anxiety.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Anxiety Agents / metabolism
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Binding Sites
  • Brain / metabolism
  • Excitatory Amino Acid Antagonists / metabolism*
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Ligands*
  • Pain / drug therapy
  • Pain / metabolism
  • Pyridines / therapeutic use
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism


  • Anti-Anxiety Agents
  • Excitatory Amino Acid Antagonists
  • Ligands
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • 6-methyl-2-(phenylethynyl)pyridine