BW1003C87 AND NBQX BUT NOT CGS19755 REDUCE GLUTAMATE RELEASE AND CEREBRAL ISCHEMIC NECROSIS

This study examines the relationship between the concentration of extr acellular glutamate released during 30 min of forebrain ischemia, and the subsequent development of ischemic neural necrosis, in the presenc e of three agents which act at distinct sites on the glutamatergic syn apse: a presynaptic inhibitor of glutamate release (5-(2,3,5-trichloro phenyl)-2,4-diamino -pyramidine ethane sulphonate (BW1003C87)); a comp etitive NMDA receptor antagonist (cis-4-phosphonomethyl-2-piperidine c arboxylic acid (CGS 19755)); and a competitive AMPA receptor antagonis t -dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX)). Pretreat ment with either BW1003C87 or NBQX markedly attenuated the peak concen tration of extracellular glutamate and offered protection from post-is chemic neuronal necrosis in the CA1 hippocampus. In contrast, pretreat ment with CGS19755 had no effect on extracellular glutamate release an d did not protect CA1 hippocampal neurons from ischemic injury.