FENAMATES PROTECT NEURONS AGAINST ISCHEMIC AND EXCITOTOXIC INJURY IN CHICK-EMBRYO RETINA

Three fenamates (flufenamate, meclofenamate and mefenamate) were exami ned for their protective effect on neurons under ischemic (glucose/oxy gen deprivation) or excitotoxic conditions, using the isolated retina of chick embryo as a model. Retinal damage was evaluated by histology and lactate dehydrogenase assay. Whole-cell recording was used to exam ine the direct effect of the fenamates on glutamate receptor-mediated currents. The fenamates protected the retina against the ischemic or e xcitotoxic insult. Part of the neuroprotection by the fenamates derive d from inhibition of N-methyl-D-aspartate receptor-mediated currents. However, kainate receptor-mediated currents were not blocked by the fe namates, which nonetheless reduced kainate receptor-mediated retinal d amage. Our results raise the possibility that fenamates may serve as l ead structures in the development of novel therapeutic agents against brain ischemia. (C) 1998 Published by Elsevier Science Ireland Ltd.