2. Academic Validation
  3. The effect of mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices

The effect of mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices

  • Eur J Pharmacol. 2006 May 1;536(3):262-8. doi: 10.1016/j.ejphar.2006.02.003.
Feng Liu 1,  Guoming Zhang,  Geoffrey Hornby,  Dmytro Vasylyev,  Mark Bowlby,  Kaapjoo Park,  Adam Gilbert,  Karen Marquis,  Terrance H Andree
Affiliations

Affiliation

  • 1 Wyeth Neuroscience Discovery Research, CN 8000, Princeton, NJ 08543, USA. [email protected]
PMID: 16600209 DOI: 10.1016/j.ejphar.2006.02.003
Abstract

Positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGlu5) have promising therapeutic potential. The effects of selective mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices have not been previously reported. The current study demonstrated that the selective mGlu5 receptor positive allosteric modulator, N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2yl)-methyl]phenyl}-2-hydrobenzamide (CPPHA) potentiated the response to a subthreshold concentration of 3,5-dihydroxy-phenylglycine (DHPG) on extracellular signal-regulated protein kinase (ERK) and cyclic-AMP responsive element-binding protein (CREB) activity, as well as N-methyl d-aspartate (NMDA) receptor subunit NR1 phosphorylation in cortical and hippocampal slices. These results suggest that allosteric modulators of mGlu5 receptor could have physiologically significant effects by potentiating the actions of glutamate.

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