Neuroprotective effects of the glutamate release inhibitor 619C89 in temporary middle cerebral artery occlusion.

Abstract

619C89 is a use-dependent Na+ channel antagonist that decreases the release of glutamate during ischemia. The efficacy of this drug in reducing infarction volume 72 h after occlusion of the middle cerebral artery (MCA) for 2 h in rats (n = 93) was determined by analysis of TTC-stained coronal section of the brain. Doses of 10, 20, 30 and 50 mg/kg of study drug given i.v. prior to MCA occlusion significantly (P < 0.05-0.01) reduced infarction volume in cortex compared to vehicle controls. Only the 50 mg/kg dose reduced infarction volume in the striatum (P < 0.05). Administration of 50 mg/kg of 619C89 30 and 60 min after the onset of ischemia reduced cortical infarction volume (P < 0.05), but there was no effect when the drug was given 5 min after reperfusion. No post-treatment regimen reduced striatal infarction volume. These results confirm the neuroprotective effects of 619C89 in temporary focal ischemia.

• Authors: K Kawaguchi, S H Graham
• Journal: Brain research (Brain Res) Vol. 749 Issue 1 Pg. 131-4 (Feb 21 1997) ISSN: 0006-8993 [Print] Netherlands
• PMID: 9070637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Neuroprotective Agents
• Piperazines
• Pyrimidines
• sipatrigine

Topics

• Animals
• Blood Gas Analysis
• Cerebral Arteries (physiology)
• Cerebral Infarction (pathology)
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Antagonists (pharmacology)
• Ischemic Attack, Transient (pathology)
• Male
• Neostriatum (pathology)
• Neuroprotective Agents (pharmacology)
• Piperazines (pharmacology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (pathology)