title: Protection by eliprodil against excitotoxicity in cultured rat retinal ganglion cells.
abstract: OBJECTIVE
  To test whether eliprodil (SL 82.0715), a unique antagonist for the N-methyl-D-aspartate (NMDA) receptor, is protective in the glutamate-induced cytotoxicity model in cultured rat retinal ganglion cells (RGCs).
  
  
  METHODS
  Two to four days after a fluorescent dye, Di-I, was injected near the superior colliculi, neonatal rats were killed, and retinal cells were dissociated and cultured. Survival of RGCs after drug treatment was assayed by counting Di-I fluorescent cells.
  
  
  RESULTS
  In rat RGCs, glutamate-induced toxicity with a mean EC50 of 10.7 microM. Only 47% of RGCs survived after a 3-day treatment with 100 microM glutamate. Studies using selective agonists and antagonists indicated that the glutamate-induced toxicity was mediated largely by the NMDA receptor. Pretreatment with eliprodil protected against such toxicity. Eliprodil exhibited a mean IC50 of 1.0 nM (log [IC50] = -9.00 +/- 0.01, mean +/- SEM, n = 3; against cell death produced by 100 microM glutamate). At 1 microM, eliprodil was maximally protective; cell survival in the presence of 100 microM glutamate challenge was 100% +/- 5% (n = 3). This protective effect of eliprodil may be related to its reduction (by 78%) of NMDA-induced currents recorded under patch-clamp recording in these cells.
  
  
  CONCLUSIONS
  Eliprodil is protective against glutamate cytotoxicity in retinal neurons. It may be a useful novel compound for the treatment of retinopathies including glaucoma in which excitotoxicity has been implicated.
authors.affiliation: Alcon Laboratories, Fort Worth, Texas 76134, USA.
authors.forename: I H
authors.initials: IH
authors.lastname: Pang
authors.forename: E M
authors.initials: EM
authors.lastname: Wexler
authors.forename: S
authors.initials: S
authors.lastname: Nawy
authors.forename: L
authors.initials: L
authors.lastname: DeSantis
authors.forename: M A
authors.initials: MA
authors.lastname: Kapin
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations; D004553:Electric Conductivity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D004338:Drug Combinations; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D018698:Glutamic Acid; D016202:N-Methylaspartate; D005998:Glycine; C058083:eliprodil