Effects of glycine antagonists in an acute in vitro electrophysiological model of ischemia

The effects of several glycine antagonists at the strychnine-insensitive si te on N-methyl-D-aspartate (NMDA) receptors in an acute in vitro electrophy siological model of ischemia in the rat hippocampus were studied. Hippocamp al slices were subjected to 9 min of hypoxia and hypoglycemia (ischemia). T he noncompetitive NMDA antagonist MK-801 produced significant protection of the slices, whereas the competitive NMDA antagonist D-CPP did not. Adminis tration of the strychnine-insensitive glycine-modulatory site antagonists ( ACEA 1021, GV150,526A, and L701,324) up to 10 mu M did not result in signif icant recovery of function. Other animal models have suggested that glycine antagonists are beneficial 6-48 hours after ischemic insult; this model as sayed functional recovery for only 1 hour after the insult. Therefore, we c onclude that this acute in vitro electrophysiologic model may not be useful in detecting the potential neuroprotective properties of glycine antagonis ts. (C) 1999 Wiley-Liss, Inc.