JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist

@article{Lavreysen2004JNJ16259685AH,
  title={JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist},
  author={Hilde Lavreysen and Ria Wouters and François Bischoff and Sandrina N{\'o}brega Pereira and Xavier Langlois and Saskia Blokland and Marijke V F Somers and Lieve Dillen and Anne Simone Josephine Lesage},
  journal={Neuropharmacology},
  year={2004},
  volume={47},
  pages={961-972}
}
Pharmacological Characterization of a New, Orally Active and Potent Allosteric Metabotropic Glutamate Receptor 1 Antagonist, 4-[1-(2-Fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC)
TLDR
FTIDC is a highly potent and selective allosteric mGluR1 antagonist and a compound having oral activity without species differences in its antagonistic activity on recombinant human, mouse, and rat mGlamR1 and could be a valuable tool for elucidating the functions of mGLUR1 not only in rodents but also in humans.
Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.
TLDR
The relationship between receptor occupancy and in vivo pharmacological activity of mGluR1 antagonists was clarified and receptor occupancy assays could help provide guidelines for selecting appropriate doses of allosteric mGLUR1 antagonist for examining the function of mR1 in vivo.
JNJ16259685, a selective mGlu1 antagonist, suppresses isolation-induced aggression in male mice.
Pharmacological Effects of the Metabotropic Glutamate Receptor 1 Antagonist Compared with Those of the Metabotropic Glutamate Receptor 5 Antagonist and Metabotropic Glutamate Receptor 2/3 Agonist in Rodents: Detailed Investigations with a Selective Allosteric Metabotropic Glutamate Receptor 1 Antago
TLDR
Investigation of the functional roles of metabotropic glutamate receptor (mGluR) 1 in integrative brain functions showed antipsychotic-like effects without impairing motor functions, whereas blockade of mGLUR5 and activation of mgluR2/3 did not display such activities.
Morphine in Combination with Metabotropic Glutamate Receptor Antagonists on Schedule-Controlled Responding and Thermal Nociception
TLDR
The results suggest that an mGlu1 and anmGlu2/3 receptor antagonist, but not an mTglu5 receptor antagonists, selectively enhance the antinociceptive effects of morphine.
Synthesis and characterization of two pet radioligands for the metabotropic glutamate 1 (mGlu1) receptor
TLDR
Evaluated two selective mGlu1 antagonists [11C]3 and [18F]4 as potential PET radioligands for the in vivo imaging of the mGLU1 receptor, finding the highest activity level was found in the cerebellum, followed by striatum, hippocampus, frontal cortex, and medulla, in a pattern consistent with the distribution of mGLu1 receptor in rat.
Development of N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methyl-4-[11C]methylbenzamide for positron emission tomography imaging of metabotropic glutamate 1 receptor in monkey brain.
TLDR
In vitro autoradiography using rat brain sections showed that [(11)C]4 binding was consistent with the distribution of mGlu1, with high specific binding in the cerebellum and thalamus, suggesting a useful PET ligand for the imaging and quantitative analysis of m Glu1 in monkey brain and merits further evaluation in humans.
Type-1, but Not Type-5, Metabotropic Glutamate Receptors are Coupled to Polyphosphoinositide Hydrolysis in the Retina
TLDR
The data provide the first example of a tissue in which a biochemically detectable PI response is mediated by mGlu1, but not mGlam5, receptors, and bovine retinal slices might be used as a model for the functional screening of mGLU1 receptor ligands.
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