Summary.
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 mGlu5 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 mGlu5 receptors as a potentially important therapeutic target particularly for the treatment of pain and anxiety.
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Received July 2, 2001 Accepted August 6, 2001 Published online September 10, 2002
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Kuhn, R., Pagano, A., Stoehr, N. et al. In vitro and in vivo characterization of MPEP, an allosteric modulator of the metabotropic glutamate receptor subtype 5: Review article. Amino Acids 23, 207–211 (2002). https://doi.org/10.1007/s00726-001-0130-6
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DOI: https://doi.org/10.1007/s00726-001-0130-6