Discovery of Allosteric Potentiators for the Metabotropic Glutamate 2 Receptor: Synthesis and Subtype Selectivity of N-(4-(2-Methoxyphenoxy)phenyl)-N-(2,2,2− trifluoroethylsulfonyl)pyrid-3-ylmethylamine
2003
This report describes recently discovered novel allosteric modulators of metabotropic glutamate2 (mGlu2) receptors. These pyridylmethylsulfonamides (e.g., 3) potentiate glutamate, shifting agonist potency by 2-fold. This effect was specific for mGlu2 (vs mGlu1,3−8 receptors). Also, 3 failed to potentiate a chimeric mGlu2/1 receptor, demonstrating the mGlu2 transmembrane region's critical involvement. In a fear-potentiated startle model, 3 showed anxiolytic activity that was prevented by mGlu2/3 antagonist pretreatment. Thus, these pyridylmethylsulfonamides represent the first mGlu2 receptor potentiators discovered.
Keywords:
- Metabotropic glutamate receptor 7
- Metabotropic glutamate receptor 2
- Metabotropic glutamate receptor 4
- Biochemistry
- Metabotropic glutamate receptor 3
- Metabotropic glutamate receptor 5
- Pharmacology
- Metabotropic glutamate receptor 6
- Stereochemistry
- Metabotropic glutamate receptor
- Chemistry
- Metabotropic glutamate receptor 1
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