A comparison of the effects of a sodium channel blocker and an NMDA antagonist upon extracellular glutamate in rat focal cerebral ischemia.

Agents such as 619C89 decrease extracellular glutamate concentrations by a primary action at voltage sensitive sodium channels, but NMDA antagonists also have been shown to decrease extracellular glutamate concentration after ischemia. To address the question as to whether 619C89's effect upon extracellular glutamate concentrations is any different than the effect of the NMDA antagonist dextrorphan, 24 rats were given either optimally neuroprotective doses of these drugs or saline prior to middle cerebral artery occlusion. In caudate, the 619C89-treated, but not dextrorphan-treated rats had less microdialysate glutamate than ischemic controls. In cortex, both 619C89- and dextrorphan-treated groups had significantly decreased glutamate compared with ischemic controls. These results support a specific effect of 619C89 upon glutamate release in caudate but not cortex.