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 microM, 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 microM 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.
Nozawa
M
M
Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Japan.
Toki
S
S
Matsuda
Y
Y
D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects*; D016923:Cell Death; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects; D016318:Quisqualic Acid / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000873:Anthracenes; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D016318:Quisqualic Acid; D007608:Kainic Acid