Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of 2-deoxyglucose (2DG) uptake and CA1 field potentials induced by hypoxia and hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to the findings obtained with pentobarbital and idebenone. Hippocampal and cortical slices were exposed to 15-20 min of ischemia, and then these slices were returned to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM KCl-induced 2DG uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals in the hippocampus. Pretreatment of nebracetam at 1 mM or pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field potentials under the condition of ischemia. In addition, nebracetam and pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus under hypoxia for 45 min. Furthermore, these drugs also attenuated the decline of 2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The present result suggests that nebracetam and pentobarbital exert neuroprotective actions against not only ischemia but also glutamate toxicity.