Department of Pharmacy, Hebei University of Science and Technology, Shijiazhuang, China.
Hebei University of Science and Technology, Shijiazhuang, China.
J Neurosci Res. 2021 Dec;99(12):3204-3221. doi: 10.1002/jnr.24937. Epub 2021 Oct 21.
Much evidence has proved that excitotoxicity induced by excessive release of glutamate contributes largely to damage caused by ischemia. In view of the key role played by NMDA receptors in mediating excitotoxicity, compounds against NMDA receptors signaling pathways have become the most promising type of anti-stroke candidate compounds. However, the limited therapeutic time window for neuroprotection is a key factor preventing NMDA receptor-related compounds from showing efficacy in all clinical trials for ischemic stroke. In this perspective, the determination of therapeutic time windows of these kinds of compounds is useful in ensuring a therapeutic effect and accelerating clinical application. This mini-review discussed the therapeutic time windows of compounds against NMDA receptors signaling pathways, described related influence factors and the status of clinical studies. The purpose of this review is to look for compounds with wide therapeutic time windows and better clinical application prospect.
大量证据表明，谷氨酸过度释放引起的兴奋毒性对缺血引起的损伤有很大贡献。鉴于 NMDA 受体在介导兴奋毒性中的关键作用，针对 NMDA 受体信号通路的化合物已成为最有前途的抗中风候选化合物类型。然而，神经保护的治疗时间窗有限是阻止 NMDA 受体相关化合物在所有缺血性中风临床试验中显示疗效的关键因素。从这个角度来看，确定这类化合物的治疗时间窗有助于确保治疗效果并加速临床应用。本综述讨论了针对 NMDA 受体信号通路的化合物的治疗时间窗，描述了相关影响因素和临床研究现状。本综述的目的是寻找治疗时间窗较宽且具有更好临床应用前景的化合物。
