Glycine site NMDA receptor antagonists provide protection against ischemia-induced neuronal damage in hippocampal slice cultures

Brain Res. 1995 Mar 27;675(1-2):38-44. doi: 10.1016/0006-8993(95)00039-s.


Ischemia-induced neuronal injury can be reduced by glutamate antagonists acting at the N-methyl-D-aspartate (NMDA) receptor. 7-Chlorokynurenic acid and the recently synthesized compound Acea 1021 block NMDA receptors by acting at the strychnine-insensitive glycine site. The anti-ischemic properties of these compounds were tested by evaluating their ability to reduce CA1 neuronal damage in hippocampal slice cultures deprived of oxygen and glucose. Acea 1021 and 7-chlorokynurenic acid significantly reduced CA1 injury produced by oxygen and glucose deprivation in a dose-dependent manner. The neuroprotective effect of these compounds was reversed by the addition of glycine. The phencyclidine site NMDA antagonist MK-801 also provided significant protection to CA1 neurons against the same insult, and this protection was not affected by the addition of glycine. These results indicate that Acea 1021 and 7-chlorokynurenic acid can provide protection to CA1 neurons against ischemia-induced injury by a glycine-sensitive mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy
  • Brain Ischemia / pathology*
  • Cell Death / drug effects
  • Dizocilpine Maleate / pharmacology
  • Glycine / pharmacology
  • Glycine Agents / pharmacology*
  • Hippocampus / pathology*
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • Neurons / drug effects*
  • Organ Culture Techniques
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glycine / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Glycine Agents
  • Quinoxalines
  • Receptors, Glycine
  • Receptors, N-Methyl-D-Aspartate
  • licostinel
  • Dizocilpine Maleate
  • Kynurenic Acid
  • 7-chlorokynurenic acid
  • Glycine