Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models

  title={Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models},
  author={Atsuyuki Kohara and Masayasu Takahashi and Shin-ichi Yatsugi and Seiji Tamura and Yoshitsugu Shitaka and Satoshi Hayashibe and Shigeki Kawabata and Masamichi Okada},
  journal={Brain Research},
Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.
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.
Selective mGluR1 Antagonist EMQMCM Inhibits the Kainate-Induced Excitotoxicity in Primary Neuronal Cultures and in the Rat Hippocampus
The obtained results indicate that the mGluR1 antagonist, EMQMCM, may exert neuroprotection against excitotoxicity after delayed treatment (30 min to 6 h).
Upregulation of Striatal Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Rats with Excessive Glutamate Release Induced by N-Acetylcysteine
Density of mGluR1 is rapidly upregulated by increases in basal Glu concentration, suggesting that mGLUR1 might to be a potential biomarker of abnormal conditions in the brain.
In Vivo Measurement of the Affinity and Density of Metabotropic Glutamate Receptor Subtype 1 in Rat Brain Using 18F-FITM in Small-Animal PET
This study is the first to the authors' knowledge to measure the in vivo affinity (Kd and binding potential) of 18F-FITM and mGluR1 density (Bmax) with a high correlation to in vitro values in rat brain regions.
Improved Visualization and Specific Binding for Metabotropic Glutamate Receptor Subtype 1 (mGluR1) Using [11C]ITMM with Ultra-High Specific Activity in Small-Animal PET
Improve visualization and threshold of specific binding for mGluR1 using [11C]ITMM with ultra-high specific activity (SA) of > 3,500 GBq/μmol in rat brains is aimed at.
Noninvasive Quantification of Metabotropic Glutamate Receptor Type 1 with [11C]ITDM: a Small-Animal PET Study
[11C]ITDM-PET is a promising tool for in vivo quantification of mGluR1 expression, demonstrating its accuracy using Huntington disease model R6/2 mice and finding a close correlation between changes in radioactive signal intensity and degree of m GluR 1 expression.
Effects of mGluR5 positive and negative allosteric modulators on brain damage evoked by hypoxia-ischemia in neonatal rats.
In 7-day-old rats, the bidirectional modulation of mGluR5 by fenobam (10 mg/kg) and ADX47273 (all doses tested) did not result in significant changes in H-I-evoked brain damage, supporting the previous data indicating that also the antagonists of MPEP and MTEP, which reduce neuronal lesions in adult animals submitted to brain ischemia, were ineffective in 7- day-old rat pups.
A glutamate receptor antagonist, S-4-carboxyphenylglycine (S-4-CPG), inhibits vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice [corrected].
S-4-CPG was not toxic and is a potential therapeutic agent for vasospasm after SAH and resulted in a trend toward improvement of animal behavior.


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
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.
Metabotropic Glutamate Receptor Subtypes as Targets for Neuroprotective Drugs
  • V. Bruno, G. Battaglia, F. Nicoletti
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2001
A series of observations suggest a potential application of mGlu5 receptor antagonists in chronic neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer disease.
[3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists.
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.
Selective Blockade of Type-1 Metabotropic Glutamate Receptors Induces Neuroprotection by Enhancing Gabaergic Transmission
Results indicate that selective blockade of mGlu1 receptors produces neuroprotection by enhancing inhibitory postsynaptic currents in GABAergic transmission.
Neuroprotective Actions of Novel and Potent Ligands of Group I and Group II Metabotropic Glutamate Receptors
Novel and selective antagonists of mGLU1 and mGlu5 were found to show consistent neuroprotective effects against N‐methyl‐d‐aspartate (NMDA)‐induced excitotoxicity in vitro and in vivo.