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丙戊酸钠:一种新型抗癫痫药物的神经保护潜力。

Cenobamate: Neuroprotective Potential of a New Antiepileptic Drug.

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie 9, 85-090, Bydgoszcz, Poland.

出版信息

Neurochem Res. 2021 Mar;46(3):439-446. doi: 10.1007/s11064-020-03188-8. Epub 2020 Nov 30.

Abstract

Central nervous system (CNS) injuries annually afflict approximately 2.7 million people in United States only, inflicting costs of nearly 100 billion US dollars. The gravity of this problem is a consequence of severe and prolonged disability of patients due to a scarce regeneration of CNS, along with the lack of efficient neuroprotective and neuroregenrative therapies. Therefore, the first and most important task in managing the CNS injury is reduction of the damaged area, and apoptosis of neurons occurs not only during the trauma, but in great extent within the following minutes and hours. This process, called secondary injury phase, is a result of trauma-induced metabolic changes in nervous tissue and neuron apoptosis. Cenobamate is a new antiepileptic drug approved by FDA on November 21, 2019. Regardless of its primary purpose, cenobamate, as a blocker of voltage-gated sodium channels and positive modulator of GABAa receptors, it appears to be a promising neuroprotective agent. Moreover, through activation of PI3K/Akt-CREB-BDNF pathway, it leads to the increase of anti-apoptotic factor levels and the decrease of pro-apoptotic factor levels, which induce inhibition of apoptosis and increase neuron survival. Similarly to riluzole, cenobamate could be an important part of a perioperative procedure in neurosurgery, decreasing the occurrence of neurological deficits. Provided that cenobamate will be effective in aforementioned conditions, it could improve treatment outcomes of millions of patients every year, thereby an extensive investigation of its efficacy as a neuroprotective treatment after central nervous system trauma should follow.

摘要

中枢神经系统(CNS)损伤每年仅在美国就影响约 270 万人,造成近 1000 亿美元的损失。由于 CNS 再生能力差,加上缺乏有效的神经保护和神经再生疗法,患者会出现严重和长期的残疾,这是造成该问题严重性的原因。因此,管理 CNS 损伤的首要和最重要的任务是减少受损区域,神经元凋亡不仅发生在创伤期间,而且在接下来的几分钟和几小时内也会大量发生。这个过程称为继发性损伤阶段,是创伤引起的神经组织代谢变化和神经元凋亡的结果。依诺巴比妥是一种新型抗癫痫药物,于 2019 年 11 月 21 日获得 FDA 批准。无论其主要用途如何,依诺巴比妥作为电压门控钠离子通道阻断剂和 GABAa 受体正向调节剂,似乎是一种很有前途的神经保护剂。此外,通过激活 PI3K/Akt-CREB-BDNF 通路,它会导致抗凋亡因子水平的增加和促凋亡因子水平的降低,从而诱导凋亡抑制和神经元存活增加。与利鲁唑类似,依诺巴比妥可能是神经外科围手术期的重要组成部分,可以降低神经功能缺损的发生。如果依诺巴比妥在上述情况下有效,它可以每年改善数百万患者的治疗效果,因此应该对其作为 CNS 创伤后神经保护治疗的疗效进行广泛研究。

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