Amitriptyline prevents N-methyl-D-aspartate (NMDA)-induced toxicity, does not prevent NMDA-induced elevations of extracellular glutamate, but augments kainate-induced elevations of glutamate.
Amitriptyline prevents N-methyl-D-aspartate (NMDA)-induced toxicity, does not prevent NMDA-induced elevations of extracellular glutamate, but augments kainate-induced elevations of glutamate.
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阿米替林可预防 N-甲基-D-天冬氨酸 (NMDA) 诱导的毒性，不会阻止 NMDA 诱导的细胞外谷氨酸升高，但会增强红藻氨酸诱导的谷氨酸升高。
DOI：
10.1111/j.1471-4159.1992.tb09385.x
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发表时间：
1992
影响因子：
4.7
通讯作者：
Smith,TG
中科院分区：
文献类型：
--
作者：
McCaslin,PP;Yu,XZ;Ho,IK;Smith,TG
研究阿米替林对红藻氨酸和N-甲基-D-天冬氨酸（NMDA）诱导的小脑颗粒神经元毒性和氨基酸释放的影响。阿米替林、丙咪嗪和去甲替林对NMDA诱导毒性的ED 50分别为6.9、6.5和1.3 μM。这些化合物都不能防止红藻氨酸诱导的毒性。尽管阿米替林对NMDA诱导的毒性具有保护作用，但其对NMDA诱导的这些细胞中谷氨酸或天冬氨酸细胞外水平的升高没有影响，表明NMDA受体活化（如谷氨酸含量升高所示）与NMDA诱导的毒性之间存在分离。然而，红藻氨酸盐和使君子酸盐处理导致谷氨酸盐和牛磺酸水平升高，其在25 μMamitriptyline存在下进一步增加。这些发现证实了其他人的报告，即三环类抗抑郁药具有与NMDA受体相关的神经保护作用，并通过显示即使有针对毒性的保护，NMDA受体仍然被激活来扩展这些报告，这表明这些化合物参与了从受体移除的位点。此外，这是第一份显示三环类抗抑郁药与非NMDA受体功能相互作用的报告。
The effect of amitriptyline on kainate‐ andN‐methyl‐D‐aspartate (NMDA)‐induced toxicity and release of amino acids from cerebellar granule neurons was studied. The ED50for amitriptyline, imipramine, and nortriptyline protection against NMDA‐induced toxicity was 6.9, 6.5, and 1.3 μM, respectively. None of these compounds protected against kainate‐induced toxicity. Even though amitriptyline was protective against NMDA‐induced toxicity, it had no effect on the NMDA‐induced increase in extracellular levels of glutamate or aspartate from these cells, indicating a dissociation between NMDA receptor activation (as indicated by glutamate content elevations) and NMDA‐induced toxicity. However, kainate and quisqualate treatment resulted in elevations of glutamate and taurine levels that were further augmented in the presence of 25 μMamitriptyline. These findings confirm the reports of others that tricyclic antidepressants have neuroprotective effects related to the NMDA receptor and expand on these reports by showing that even though there is protection against toxicity, the NMDA receptor is nevertheless activated, suggesting an involvement of these compounds at sites removed from the receptor. Furthermore, this is the first report showing an interaction of tricyclic antidepressants with the function of non‐NMDA receptors.