Over-additive protective effect of dizocilpine and NBQX against neuronal damage.
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.
Lippert
K
K
Institut für Pharmacokologie und Toxikologie, Fachbereich Pharmazie und Lebensmittelchemie, Philipps-Universität, Marburg, Germany.
Welsch
M
M
Krieglstein
J
J
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*
D005971:Glutamates; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018698:Glutamic Acid; D016291:Dizocilpine Maleate