Fenamates protect neurons against ischemic and excitotoxic injury in chick embryo retina.
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.
Chen
Q
Q
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Olney
J W
JW
Lukasiewicz
P D
PD
Almli
T
T
Romano
C
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy*; D002642:Chick Embryo; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005439:Flufenamic Acid / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D008528:Mefenamic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005439:Flufenamic Acid; D005947:Glucose; D007608:Kainic Acid; D008469:Meclofenamic Acid; D008528:Mefenamic Acid; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010100:Oxygen; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D062367:ortho-Aminobenzoates; C001209:fenamic acid