dizocilpine-maleate and fenamic-acid

Three fenamates (flufenamate, meclofenamate and mefenamate) were examined for their protective effect on neurons under ischemic (glucose/oxygen 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 examine the direct effect of the fenamates on glutamate receptor-mediated currents. The fenamates protected the retina against the ischemic or excitotoxic insult. Part of the neuroprotection by the fenamates derived from inhibition of N-methyl-D-aspartate receptor-mediated currents. However, kainate receptor-mediated currents were not blocked by the fenamates, which nonetheless reduced kainate receptor-mediated retinal damage. Our results raise the possibility that fenamates may serve as lead structures in the development of novel therapeutic agents against brain ischemia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain Ischemia; Chick Embryo; Dizocilpine Maleate; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Flufenamic Acid; Glucose; Kainic Acid; Meclofenamic Acid; Mefenamic Acid; N-Methylaspartate; Neuroprotective Agents; Neurotoxins; Organ Culture Techniques; ortho-Aminobenzoates; Oxygen; Patch-Clamp Techniques; Receptors, AMPA; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate; Retinal Ganglion Cells