A DOSE-RESPONSE STUDY OF NEUROPROTECTION USING THE AMPA ANTAGONIST NBQX IN RAT FOCAL CEREBRAL-ISCHEMIA

AMPA antagonists have been shown to be remarkably neuroprotective in m odels of global ischemia, but the data in focal ischemia remain contro versial. We, therefore, studied the dose-response characteristics and the time window of efficacy of the AMPA antagonist NBQX in a rat model of permanent focal ischemia. NBQX 40, 60 or 100 mg/kg i.v., substanti ally reduced infarct size. Neuroprotection was maintained when the ini tiation of drug administration was with held for 15, 45 or 90 min afte r permanent middle cerebral artery occlusion. Furthermore, NBQX did no t induce heat shock protein in cingulate cortex, as do some N-methyl-D -aspartate antagonists. Thus, the compound is a potent neuroprotectant in focal ischemia and has an unusually long time window of effectiven ess.