Add time:08/19/2019         Source:sciencedirect.com

To address the issue of the cytotoxicity of glutamate antagonists, we administered representative agents to rats and used HSP72 immunocytochemistry as a measure of neuronal injury in the brain. The doses studied spanned the reported neuroprotective range for each compound. Some, but not all, glutamate antagonists induce neuronal injury in the brain. The non-competitive NMDA antagonists (MK801 and dextrorphan) demonstrate maximum toxicity. Competitive NMDA antagonists (CGS 19755 and MDL 100,453) may or may not induce neuronal injury depending on the particular compound. The polyamine site (SL 82.0715-10) antagonist does not result in neuronal injury. Cingulate and retrosplenial cortex neurotoxicity is not a ubiquitous feature of neuroprotective agents that block excitotoxcity, but is limited to NMDA antagonists and may depend upon the duration and completeness of the blockade of the NMDA receptor.

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