School of Life Sciences, University of Glasgow, Glasgow, UK.
Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA, USA; Department of Pharmacology, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Neuropharmacology. 2020 May 15;168:107966. doi: 10.1016/j.neuropharm.2020.107966. Epub 2020 Jan 14.
Antiseizure drugs (ASDs) prevent the occurrence of seizures; there is no evidence that they have disease-modifying properties. In the more than 160 years that orally administered ASDs have been available for epilepsy therapy, most agents entering clinical practice were either discovered serendipitously or with the use of animal seizure models. The ASDs originating from these approaches act on brain excitability mechanisms to interfere with the generation and spread of epileptic hyperexcitability, but they do not address the specific defects that are pathogenic in the epilepsies for which they are prescribed, which in most cases are not well understood. There are four broad classes of such ASD mechanisms: (1) modulation of voltage-gated sodium channels (e.g. phenytoin, carbamazepine, lamotrigine), voltage-gated calcium channels (e.g. ethosuximide), and voltage-gated potassium channels [e.g. retigabine (ezogabine)]; (2) enhancement of GABA-mediated inhibitory neurotransmission (e.g. benzodiazepines, tiagabine, vigabatrin); (3) attenuation of glutamate-mediated excitatory neurotransmission (e.g. perampanel); and (4) modulation of neurotransmitter release via a presynaptic action (e.g. levetiracetam, brivaracetam, gabapentin, pregabalin). In the past two decades there has been great progress in identifying the pathophysiological mechanisms of many genetic epilepsies. Given this new understanding, attempts are being made to engineer specific small molecule, antisense and gene therapies that functionally reverse or structurally correct pathogenic defects in epilepsy syndromes. In the near future, these new therapies will begin a paradigm shift in the treatment of some rare genetic epilepsy syndromes, but targeted therapies will remain elusive for the vast majority of epilepsies until their causes are identified. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
抗癫痫药物（ASD）可预防癫痫发作；但没有证据表明它们具有疾病修饰特性。在可用于癫痫治疗的口服 ASD 问世的 160 多年里，大多数进入临床实践的药物都是偶然发现的，或者是使用动物癫痫模型发现的。这些方法产生的 ASD 作用于大脑兴奋性机制，干扰癫痫过度兴奋的产生和传播，但它们并不能解决其治疗的癫痫疾病的特定缺陷，而这些缺陷在大多数情况下并未得到很好的理解。这类 ASD 机制有四大类：（1）调制电压门控钠离子通道（如苯妥英、卡马西平、拉莫三嗪）、电压门控钙离子通道（如乙琥胺）和电压门控钾离子通道[如瑞替加滨（依佐加滨）]；（2）增强 GABA 介导的抑制性神经传递[如苯二氮䓬类、噻加宾、氨己烯酸]；（3）减弱谷氨酸介导的兴奋性神经传递[如吡仑帕奈]；（4）通过突触前作用调制神经递质释放[如左乙拉西坦、布瓦西坦、加巴喷丁、普瑞巴林]。在过去的二十年中，人们在确定许多遗传性癫痫的病理生理机制方面取得了巨大进展。鉴于这一新的认识，人们正在尝试设计特定的小分子、反义寡核苷酸和基因疗法，以功能性逆转或结构纠正癫痫综合征的致病缺陷。在不久的将来，这些新疗法将开始改变一些罕见遗传性癫痫综合征的治疗模式，但在确定其病因之前，针对特定靶点的治疗方法仍难以实现，绝大多数癫痫都将如此。本文是题为“21 世纪的新型癫痫治疗方法——从抗癫痫药物到癫痫的预防、修饰和治疗”的特刊的一部分。
