Neuroprotective effects of the glutamate release inhibitor 619C89 in temporary middle cerebral artery occlusion.
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.
Kawaguchi
K
K
Department of Neurology, University of Pittsburgh, PA 15213, USA.
Graham
S H
SH
D000818:Animals; D001784:Blood Gas Analysis; D002536:Cerebral Arteries / Q000502:physiology; D002544:Cerebral Infarction / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D017072:Neostriatum / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010879:Piperazines; D011743:Pyrimidines; C081980:sipatrigine