Salt T.E.; Binns K.E.; Turner J.P.; Gasparini F., and Kuhn R. ( 1999) Antagonism of the mGlu5 agonist 2-chloro-5-hydroxyphenylglycine by the novel selective mGlu5 antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) in the thalamus. British Journal of Pharmacology, 127: 1057-1059.
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.
Full text is available at British Journal of Pharmacology.