title: Over-additive protective effect of dizocilpine and NBQX against neuronal damage.
abstract: Several reports have indicated that the two glutamate receptor antagonists, dizocilpine (that binds to the phencyclidine recognition site of the NMDA (N-methyl-D-aspartate) receptor) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline, that binds to the AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole) receptor), protect neurons against damage caused by hypoxia, ischemia or excitotoxicity. We, therefore, used a combination of these drugs to achieve enhanced neuroprotection. Primary cultures of rat hippocampal neurons were challenged by glutamate intoxication. Both dizocilpine and NBQX produced dose-dependent increases in the percentage of viable neurons. Combined treatment with both glutamate receptor antagonists had an over-additive neuroprotective effect. Simultaneous administration of dizocilpine and NBQX also had a pronounced neuroprotective effect in vivo in mice subjected to focal cerebral ischemia and rats with global forebrain ischemia. This suggest that such a combination may have therapeutic relevance.
authors.affiliation: Institut für Pharmacokologie und Toxikologie, Fachbereich Pharmazie und Lebensmittelchemie, Philipps-Universität, Marburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Lippert
authors.forename: M
authors.initials: M
authors.lastname: Welsch
authors.forename: J
authors.initials: J
authors.lastname: Krieglstein
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004357:Drug Synergism; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*
chemical_list: D005971:Glutamates; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D016291:Dizocilpine Maleate