GYKI 52466 protects against non-NMDA receptor-mediated excitotoxicity in primary rat hippocampal cultures
| Autor: | Patrick C. May, Paula M. Robison |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Agonist
medicine.drug_class Neurotoxins Excitotoxicity Kainate receptor AMPA receptor Pharmacology medicine.disease_cause Hippocampus Neuroprotection Rats Sprague-Dawley Benzodiazepines Receptors Kainic Acid Quinoxalines medicine Animals Cells Cultured 6-Cyano-7-nitroquinoxaline-2 3-dione Kainic Acid Dose-Response Relationship Drug Chemistry General Neuroscience Glutamate receptor Receptor antagonist Rats Anti-Anxiety Agents Receptors Glutamate nervous system NMDA receptor |
| Zdroj: | Neuroscience Letters. 152:169-172 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/0304-3940(93)90510-r |
| Popis: | Glutamate excitotoxicity is mediated by both N- methyl- d -aspartate (NMDA)-receptor and non-NMDA receptor (α-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA)/kainate (KA)) mechanisms but the lack of specific antagonists has limited the characterization of AMPA/KA receptormediated excitotoxicity. The 2,3-benzodiazepine GYKI 52466 is a newly described non-competitive AMPA/KA receptor antagonist. We have investigated the neuroprotective efficacy of GYKI 52466 in an embryonic rat hippocampal culture model of non-NMDA receptor-mediated excitotoxicity using KA as an agonist at the AMPA/KA receptor. Overnight treatment with 50 μM KA resulted in prominent neuronal excitotoxicity as assessed by lactate dehydrogenase efflux. GYKI 52466 attenuated KA excitotoxicity in a dose-dependent manner with an IC 50 of 9 μM. Together with competitive antagonists (e.g., various quinoxalinediones), non-competitive antagonists like GYKI 52466 can now be used to dissect mechanisms of non-NMDA receptor mediated excitotoxicity. |
| Databáze: | OpenAIRE |
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