Antagonism of the mGlu5 agonist 2-chloro-5-hydroxyphenylglycine by the novel selective mGlu5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) in the thalamus

Br J Pharmacol. 1999 Jul;127(5):1057-9. doi: 10.1038/sj.bjp.0702677.


Our previous work has shown that Group I mGlu receptors participate in thalamic sensory processing in vivo. However, unequivocal demonstration of mGlu5 participation has not been possible due to the lack of specific ligands. We have therefore made a preliminary study of the in vivo actions of the agonist (R,S)-2-Chloro-5-hydroxyphenylglycine [CHPG] and the novel mGlu5 antagonist 6-methyl-2-(phenylethynyl)-pyridine [MPEP] in order to characterize their suitability for functional studies. Iontophoretically administered MPEP selectively antagonized excitatory responses of single rat thalamic neurones to CHPG compared to the broad-spectrum mGlu agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate. In contrast, the established mGlu1 and mGlu5 antagonist (S)-4-carboxyphenylglycine reduced responses to both agonists. These findings are the first demonstration of an in vivo action of CHPG and its antagonism by a selective mGlu5 antagonist. Furthermore MPEP appears to be a good tool for functional studies of mGlu5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Phenylacetates / pharmacology*
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / drug effects*
  • Thalamus / drug effects*


  • 2-chloro-5-hydroxyphenylglycine
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Phenylacetates
  • Pyridines
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • 6-methyl-2-(phenylethynyl)pyridine
  • Glycine