THE NEUROPROTECTIVE PROPERTIES OF ES-242S, NOVEL NMDA RECEPTOR ANTAGONISTS, IN NEURONAL CELL-CULTURE TOXICITY STUDIES

ES-242-1, a novel bioxanthracene of microbial origin, blocked glutamate-induced neuronal death in a dose-dependent manner at concentrations ranging from 0.01 to 1.0 muM, but not the neuronal death caused by kainic acid or quisqualic acid. ES-242-1 also prevented cell death induced by 2,4-methanoglutamate, which is a specific agonist for the NMDA receptor. ES-242-1 showed protective effects in cultured neurons prepared from cerebellum and septum as it did in cultured hippocampal neurons but to different extents. There was a positive correlation between the potencies of ES-242s as inhibitors of ligand binding to the NMDA receptor and as inhibitors of neuronal death. Hypoxic treatment for 4 h under 95% N2 and 5% CO2 caused neuronal death of the cultured hippocampal neurons. Again, ES-242-1 at 1.0 muM was effective to protect neurons against hypoxic injury. ES-242 compounds are new chemical entities possessing neuroprotective properties useful in the treatment of diseases involving glutamate toxicity.