Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.
@article{Suzuki2009CorrelationOR, title={Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.}, author={Gentaroh Suzuki and Hiroko Kawagoe-Takaki and Takao Inoue and Toshifumi Kimura and Hirohiko Hikichi and Takashi Murai and Akio Satow and Mikiko Hata and Shunsuke Maehara and Satoru Ito and Hiroshi Kawamoto and Satoshi Ozaki and Hisashi Ohta}, journal={Journal of pharmacological sciences}, year={2009}, volume={110 3}, pages={ 315-25 } }
The aim of this study was to clarify the relationship between receptor occupancy and in vivo pharmacological activity of mGluR1 antagonists. The tritiated mGluR1-selective allosteric antagonist [(3)H]FTIDC (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) was identified as a radioligand having high affinity for mGluR1-expressing CHO cells (K(D) = 2.1 nM) and mouse cerebellum (K(D) = 3.7 nM). [(3)H]FTIDC bound to mGluR1 was…
Figures and Tables from this paper
16 Citations
Effect of CFMTI, an allosteric metabotropic glutamate receptor 1 antagonist with antipsychotic activity, on Fos expression in regions of the brain related to schizophrenia
- Psychology, BiologyNeuroscience
- 2010
Allosteric modulation of metabotropic glutamate receptors.
- Biology, ChemistryAdvances in pharmacology
- 2011
Radiosynthesis and evaluation of [11C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1.
- Biology, ChemistryNuclear medicine and biology
- 2010
Development of a β-Lactamase Reporter Gene Assay for Metabotropic Glutamate Receptor 1 by Using Coexpression of Glutamate Transporter
- Biology, ChemistryJournal of biomolecular screening
- 2010
The β-lactamase reporter assay with CHO-NFAT-bla-hmGluR1b-GLAST could be a novel high-throughput assay for mGLUR1 antagonist screening.
mGluR1 Negative Allosteric Modulators: An Alternative Metabotropic Approach for the Treatment of Schizophrenia
- Psychology, Biology
- 2010
The antippsychotic-like effects of mGluR1 NAMs are similar to those of the atypical antipsychotic, clozapine, but not of the typical antipsychotics, haloperidol, based on behavioral changes as well as distribution of c-fos expression after the treatment.
Synthesis, characterization, and monkey PET studies of [18F]MK‐1312, a PET tracer for quantification of mGluR1 receptor occupancy by MK‐5435
- Biology, ChemistrySynapse
- 2011
Results are promising for clinical PET studies with [18F]MK‐1312 to determine mGluR1 occupancy of MK‐5435 and a large specific signal useful for determination of mGLUR1 receptor occupancy in rhesus monkey is revealed.
3-Phenyl-5-isothiazole carboxamides with potent mGluR1 antagonist activity.
- ChemistryBioorganic & medicinal chemistry letters
- 2012
Synthesis and evaluation of 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain.
- Chemistry, BiologyBioorganic & medicinal chemistry
- 2011
Current Radioligands for the PET Imaging of Metabotropic Glutamate Receptors
- Biology, MedicinePET and SPECT of Neurobiological Systems
- 2020
Recent research efforts toward the development of PET radioligands for other receptor subtypes more specifically, mGluR2/mGlu R3 and mGLUR4 are outlined alongside their in vitro/in vivo properties and clinical applications where available.
Imaging of Metabotropic Glutamate Receptors (mGluRs)
- Biology
- 2012
The ubiquitous amino acid L-glutamate is thought to act as a neurotransmitter at the majority of synapses in the brain, and has been shown by mutagenesis studies to confer glutamate binding, agonist activation of the receptor, and subtype specificity for group selective agonists.
References
SHOWING 1-10 OF 43 REFERENCES
In vivo receptor occupancy of mGlu5 receptor antagonists using the novel radioligand [3H]3-methoxy-5-(pyridin-2-ylethynyl)pyridine).
- Biology, ChemistryEuropean journal of pharmacology
- 2003
[3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists.
- Biology, ChemistryMolecular pharmacology
- 2003
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.
Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models
- Biology, ChemistryBrain Research
- 2008
Antinociceptive profile of a selective metabotropic glutamate receptor 1 antagonist YM-230888 in chronic pain rodent models.
- Biology, ChemistryEuropean journal of pharmacology
- 2007
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)
- Biology, ChemistryJournal of Pharmacology and Experimental Therapeutics
- 2007
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.
Metabotropic glutamate 1 receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using [3H]R214127
- Biology, ChemistryNeuropharmacology
- 2004
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
- Biology, PsychologyJournal of Pharmacology and Experimental Therapeutics
- 2008
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.
BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity.
- Biology, ChemistryMolecular pharmacology
- 2001
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.
Radioligand Binding Properties and Pharmacological Characterization of 6-Amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-298198), a High-Affinity, Selective, and Noncompetitive Antagonist of Metabotropic Glutamate Receptor Type 1
- Biology, ChemistryJournal of Pharmacology and Experimental Therapeutics
- 2005
YM-298198 is a newly synthesized, high-affinity, selective, and noncompetitive antagonist of mGluR1 that will be a useful pharmacological tool due to its highly active properties in vitro and in vivo.
JNJ16259685, a highly potent, selective and systemically active mGlu1 receptor antagonist
- Biology, ChemistryNeuropharmacology
- 2004