A Novel Selective Allosteric Modulator Potentiates the Activity of Native Metabotropic Glutamate Receptor Subtype 5 in Rat Forebrain

  title={A Novel Selective Allosteric Modulator Potentiates the Activity of Native Metabotropic Glutamate Receptor Subtype 5 in Rat Forebrain},
  author={Julie A O'brien and Wei Lemaire and Marion Wittmann and Marlene A. Jacobson and Sookhee N. Ha and David D. Wisnoski and Craig W. Lindsley and Herv{\'e} J. Schaffhauser and Blake A. Rowe and Cyrille Sur and Mark E. Duggan and Douglas J. Pettibone and P. Jeffrey Conn and David Williams},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={568 - 577}
We found that N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA), is a potent and selective positive allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5). CPPHA alone had no agonist activity and acted as a selective positive allosteric modulator of human and rat mGluR5. CPPHA potentiated threshold responses to glutamate in fluorometric Ca2+ assays 7- to 8-fold with EC50 values in the 400 to 800 nM range, and at 10 μM… 

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Positive allosteric modulators of metabotropic glutamate 1 receptor: Characterization, mechanism of action, and binding site
  • F. Knoflach, V. Mutel, J. Kemp
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2001
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