BW1003C87 and NBQX but not CGS19755 reduce glutamate release and cerebral ischemic necrosis.
This study examines the relationship between the concentration of extracellular glutamate released during 30 min of forebrain ischemia, and the subsequent development of ischemic neural necrosis, in the presence of three agents which act at distinct sites on the glutamatergic synapse: a presynaptic inhibitor of glutamate release (5-(2,3,5-trichlorophenyl)-2,4-diamino-pyramidine ethane sulphonate (BW1003C87)); a competitive NMDA receptor antagonist (cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS19755)); and a competitive AMPA receptor antagonist (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX)). Pretreatment with either BW1003C87 or NBQX markedly attenuated the peak concentration of extracellular glutamate and offered protection from post-ischemic neuronal necrosis in the CA1 hippocampus. In contrast, pretreatment with CGS19755 had no effect on extracellular glutamate release and did not protect CA1 hippocampal neurons from ischemic injury.
Gaspary
H L
HL
Department of Neurology, University of California, School of Medicine, San Francisco 94143-0114.
Simon
R P
RP
Graham
S H
SH
D000704:Analysis of Variance; D000818:Animals; D001667:Binding, Competitive; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009336:Necrosis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D015588:Observer Variation; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000188:drug therapy
D010875:Pipecolic Acids; D011743:Pyrimidines; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C078265:5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine ethane sulfonate; D018698:Glutamic Acid; C053672:selfotel; D016202:N-Methylaspartate