Chen J, Graham S H, Simon R P
Department of Neurology, University of Pittsburgh, PA 15261, USA.
Brain Res. 1995 Nov 13;699(1):121-4. doi: 10.1016/0006-8993(95)00868-q.
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.
诸如619C89之类的药物通过对电压敏感钠通道的主要作用来降低细胞外谷氨酸浓度，但已证明NMDA拮抗剂在缺血后也可降低细胞外谷氨酸浓度。为了探讨619C89对细胞外谷氨酸浓度的影响是否与NMDA拮抗剂右啡烷的作用有所不同，在大脑中动脉闭塞前，给24只大鼠给予这些药物的最佳神经保护剂量或生理盐水。在尾状核中，接受619C89治疗而非右啡烷治疗的大鼠的微透析谷氨酸含量低于缺血对照组。在皮质中，与缺血对照组相比，接受619C89和右啡烷治疗的组的谷氨酸含量均显著降低。这些结果支持了619C89对尾状核而非皮质中谷氨酸释放具有特定作用。
