OVER-ADDITIVE PROTECTIVE EFFECT OF DIZOCILPINE AND NBQX AGAINST NEURONAL DAMAGE

Several reports have indicated that the two glutamate receptor antagon ists, dizocilpine (that binds to the phencyclidine recognition site of the NMDA (N-methyl-D-aspartate) receptor) and NBQX 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. Primar y cultures of rat hippocampal neurons were challenged by glutamate int oxication. Both dizocilpine and NBQX produced dose-dependent increases in the percentage of viable neurons. Combined treatment with both glu tamate receptor antagonists had an over-additive neuroprotective effec t. Simultaneous administration of dizocilpine and NBQX also had a pron ounced neuroprotective effect in vivo in mice subjected to focal cereb ral ischemia and rats with global forebrain ischemia. This suggest tha t such a combination may have therapeutic relevance.