Abstract
The effects of several glycine antagonists at the strychnine-insensitive site on N-methyl-D-aspartate (NMDA) receptors in an acute in vitro electrophysiological model of ischemia in the rat hippocampus were studied. Hippocampal slices were subjected to 9 min of hypoxia and hypoglycemia (ischemia). The noncompetitive NMDA antagonist MK-801 produced significant protection of the slices, whereas the competitive NMDA antagonist D-CPP did not. Administration of the strychnine-insensitive glycine-modulatory site antagonists (ACEA 1021, GV150,526A, and L701,324) up to 10 μM did not result in significant recovery of function. Other animal models have suggested that glycine antagonists are beneficial 6–48 hours after ischemic insult; this model assayed functional recovery for only 1 hour after the insult. Therefore, we conclude that this acute in vitro electrophysiologic model may not be useful in detecting the potential neuroprotective properties of glycine antagonists. Drug Dev. Res. 46:134–138, 1999. © 1999 Wiley-Liss, Inc.
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