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}
}
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118 Citations
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118 Citations

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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.
Identification of a novel transmembrane domain involved in the negative modulation of mGluR1 using a newly discovered allosteric mGluR1 antagonist, 3-cyclohexyl-5-fluoro-6-methyl-7-(2-morpholin-4-ylethoxy)-4H-chromen-4-one
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.
Pharmacological effects of metabotropic glutamate receptor ligands on prepulse inhibition in DBA/2J mice.
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.
Metabotropic Glutamate Receptors
TLDR
This chapter will focus on a brief description and summary of key findings for a number of neuropharmacologic agents for the metabotropic glutamate (mGlu) receptors.
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References

SHOWING 1-10 OF 27 REFERENCES
[3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists.
TLDR
The high affinity and selectivity of [(3)H]R214127 for mGlu1 receptors renders this compound the ligand of choice to study the native mGLU1 receptor in brain.
BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity.
TLDR
BAY36-7620 will be useful to further delineate the functional importance of the mGlu1 receptor, including its putative agonist-independent activity, andTransmembrane helices 4 to 7 are shown to play a critical role in the selectivity of BAY36- 7620.
CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding.
TLDR
It is proposed that the interaction of CPCCOEt with Thr815 and Ala818 of mGluR1 disrupts receptor activation by inhibiting an intramolecular interaction between the agonist-bound extracellular domain and the transmembrane domain.
A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5.
TLDR
Evidence that allosteric sites on GPCRs can respond to closely related ligands with a range of pharmacological activities from positive to negative modulation as well as to neutral competition of this modulation is provided.
Supersensitivity of human metabotropic glutamate 1a receptor signaling in L929sA cells.
TLDR
These results suggest that antagonist-evoked mGlu1 receptor supersensitivity is not merely the result of a blockade of agonist-induced desensitization, and are the first lines of evidence that prolonged antagonist treatment can supersensitize the hmGlu 1a receptor.
Metabotropic glutamate 1 receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using [3H]R214127
Mutational Analysis and Molecular Modeling of the Allosteric Binding Site of a Novel, Selective, Noncompetitive Antagonist of the Metabotropic Glutamate 1 Receptor*
TLDR
A striking conservation in the position of critical residues of the EM-TBPC-binding pocket of the mGlu1 receptor is observed, validating the rhodopsin crystal structure as a template for the family 3 G-protein-coupled receptors.
Neuroprotective and behavioral effects of the selective metabotropic glutamate mGlu(1) receptor antagonist BAY 36-7620.
Synthesis and pharmacological characterisation of 2,4-dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists.
Pharmacological characterization of metabotropic glutamate receptors in several types of brain cells in primary cultures.
TLDR
The data show that mGLUR2- and mGluR3-like receptors can directly inhibit AC in neurons, and they raise the question of whether mgluR4 is really negatively coupled to AC in its normal environment, and there is evidence for a new mGLuR subtype expressed in glial cells.
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