licostinel and 7-chlorokynurenic-acid

Topics: Animals; Cerebral Cortex; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Kainic Acid; Kynurenic Acid; N-Methylaspartate; Potassium Chloride; Quinoxalines; Rats; Receptors, N-Methyl-D-Aspartate; Spinal Cord; Synaptic Transmission

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.

Topics: Animals; Brain Ischemia; Cell Death; Dizocilpine Maleate; Glycine; Glycine Agents; Hippocampus; Kynurenic Acid; Neurons; Organ Culture Techniques; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Glycine; Receptors, N-Methyl-D-Aspartate