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

Abstract

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.

• Authors: D W Newell, A Barth, A T Malouf
• Journal: Brain research (Brain Res) Vol. 675 Issue 1-2 Pg. 38-44 (Mar 27 1995) ISSN: 0006-8993 [Print] Netherlands
• PMID: 7796152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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