Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective

V. Bruno, I. Ksiazek, G. Battaglia, S. Lukic, T. Leonhardt, D. Sauer, F. Gasparini, R. Kuhn, F. Nicoletti, P. J. Flor

Research output: Contribution to journalArticlepeer-review


We have used potent and selective non-competitive antagonists of metabotropic glutamate receptor subtype 5 (mGlu5) -- 2-methyl-6-phenylethynylpyridine (MPEP), [6-methyl-2-(phenylazo)-3-pyridinol] (SIB-1757) and [(E)-2-methyl-6-(2-phenylethenyl)pyridine] (SIB-1893) - to examine whether endogenous activation of this particular metabotropic glutamate receptor subtype contributes to neuronal degeneration. In cortical cultures challenged with N-methyl-D-aspartate (NMDA), all three mGlu5 receptor antagonists were neuroprotective. The effect of MPEP was highly specific because the close analogue, 3-methyl-6-phenylethynylpyridine (iso-MPEP), which did not antagonize heterologously expressed mGlu5 receptors, was devoid of activity on NMDA toxicity. Neuroprotection by mGlu5 receptor antagonists was also observed in cortical cultures challenged with a toxic concentration of β-amyloid peptide. We have also examined the effect of mGlu5 receptor antagonists in in vivo models of excitotoxic degeneration. MPEP and SIB-1893 were neuroprotective against neuronal damage induced by intrastriatal injection of NMDA or quinolinic acid. These results indicate that mGlu5 receptors represent a suitable target for novel neuroprotective agents of potential application in neurodegenerative disorders. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)2223-2230
Number of pages8
Issue number12
Publication statusPublished - Nov 2000


  • β-Amyloid toxicity
  • Excitotoxicity
  • mGlu5 receptors
  • MPEP
  • Neuroprotection
  • Non-competitive antagonists
  • SIB-1757
  • SIB-1893

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology


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