从已知药物中挖掘具有抗癫痫作用的药物（老药新用）是癫痫药物发现的新契机。Nav1.2选择性表达于中枢的兴奋性神经元，开发特异性阻断Nav1.2亚型的抗癫痫药有望减少传统的抗癫痫药由于缺乏亚型选择性而带来的副反应。前期申请者针对已上市药物库开展筛选工作，发现抗病毒药阿比朵尔在细胞水平能够抑制神经元癫痫样放电，在动物癫痫药效学模型上能够有效缓解癫痫发作；通过靶点识别发现阿比朵尔选择性阻断Nav1.2钠通道。这是关于阿比朵尔抗癫痫活性和钠通道抑制剂活性的首次研究发现。为阐明阿比朵尔抗癫痫作的分子药理学机制，拟应用分子生物学和电生理手段，详细研究阿比朵尔对Nav1.2生物物理学特征(状态依赖性抑制、激活、失活、去激活、持续性钠电流、分子结合位点等)以及海马神经元兴奋性的影响等。该项目有望为阿比朵尔在癫痫适应症的应用中提供科学依据，同时为开发Nav1.2抑制剂类抗癫痫新药奠定先导物基础。

Re-investigating approved drugs for new indication of epilepsy represents promising therapeutic opportunity. Traditional antiepileptic drugs targeting sodium channels often cause severe side effects due to lacking sodium subtype selectivity. Nav1.2 sodium channel specifically expresses in the excitable neurons of central nervous system, therefore has been proposed as a selective antiepileptic target providing increased therapeutic potential and fewer side effects. In previous study we identified arbidol (an anti-virus drug) with antiepileptic activity in a high throughput phenotypic screening campaign against FDA approved drug library; the effect of arbidol was confirmed in epileptic rats; in the meanwhile, we found that arbidol potently inhibited Nav1.2 channel. It was the first study to find arbidol as an antiepileptic agent with an inhibitory activity on sodium channel. To clarify the molecular mechanisms of arbidol as an anti-epileptic agent, by using molecular biology and electrophysiology approaches, the following items will be investigated, including the effects of arbidol on the biophysical properties of Nav1.2 channel (state dependent inhibition, steady state activation and inactivation, deactivation, persistent sodium current, the binding sites of the inhibitor on channel protein), and the effects of arbidol on the excitability of hippocampal neurons (resting membrane potential, action potential threshold, action potential frequency). This study will provide fundamental evidence for the application of arbidol in treating epilepsy and arbidol may serve as a lead compound for future development of antiepileptic drugs targeting Nav1.2 sodium channel.