论文部分内容阅读
癫痫是最常见的中枢神经系统疾病之一，影响世界数千万人生活。目前临床常用抗癫痫药物绝大多数是以离子类机制拮抗癫痫发作，包括作用于各种离子通道或离子通道型受体。但随着对癫痫发病机制的深入研究，非离子类抗癫痫机制越发成为各种难治性癫痫控制的关键，且相关药物已逐步实现临床转化。文中按已实现临床转化和尚处于临床前研究对各种非离子类抗癫痫机制进行分类，着重介绍相关已实现临床转化的非离子类抗癫痫药物在各种难治性癫痫中的应用，包括依维莫司、大麻二酚、芬氟拉明、帕西伏尼、中链甘油三酯改良生酮饮食、阿那白滞素等。简要介绍部分临床前阶段的非离子类抗癫痫机制如前列腺素、腺苷、代谢性谷氨酸受体、线粒体机制等。现阶段离子类抗癫痫药物研究已达到转化瓶颈，很难再实现机制上的较大突破，而许多非离子类抗癫痫机制尚未实现临床转化，有更为广阔的研究前景。从更深层次的角度看，部分非离子类抗癫痫机制可能已经涉及癫痫发生的根本机制，或许是未来治疗难治性癫痫的曙光。“,”Epilepsy is one of the most common diseases of the central nervous system, affecting tens of millions of people around the world. Most of clinically used antiepileptic drugs are based on ion mechanism to antagonize epileptic seizures, targeted to various ion channels or ion channel receptors. However, with the in-depth research on the pathogenesis of epilepsy, the non-ionic antiepileptic mechanism has increasingly become the key to the control of various intractable epilepsy, and the relevant drugs have gradually achieved clinical transformation. In this paper, non-ionic antiepileptic mechanisms are classified to clinical and preclinical types according to whether clinical transformation has been achieved. The application of non-ionic antiepileptic drugs in refractory epilepsy was mainly introduced, including everolimus, cannabidiol, fenfluramine, padsevonil, medium chain triglyceride modified ketogenic diet, and anakinra. Additionally, some preclinical non-ionic antiepileptic mechanisms such as prostaglandin, adenosine, metabolic glutamate receptor and mitochondrial mechanism are briefly introduced. The authors believe that the current stage of ionic antiepileptic drugs research has reached the bottleneck of transformation and it is difficult to achieve a major breakthrough in the mechanism, but there are broader research prospects in non-ionic antiepileptic mechanisms because a large number of them have not yet been clinically transformed. From a deeper perspective, some non-ionic antiepileptic mechanisms may have been involved in the fundamental mechanism of epileptogenesis, and they may be the prospect for the future treatment of refractory epilepsy.