Dipartimento di Neurofisiopatologia, Fondazione Istituto Neurologico C Besta, Milano, Italy.
Lancet Neurol. 2010 Apr;9(4):413-24. doi: 10.1016/S1474-4422(10)70059-4.
Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal and muscle excitability. Abnormal VGSC activity is central to the pathophysiology of epileptic seizures, and many of the most widely used antiepileptic drugs, including phenytoin, carbamazepine, and lamotrigine, are inhibitors of VGSC function. These antiepileptic drugs might also be efficacious in the treatment of other nervous system disorders, such as migraine, multiple sclerosis, neurodegenerative diseases, and neuropathic pain. In this Review, we summarise the structure and function of VGSCs and their involvement in the pathophysiology of several neurological disorders. We also describe the biophysical and molecular bases for the mechanisms of action of antiepileptic VGSC blockers and discuss the efficacy of these drugs in the treatment of epileptic and non-epileptic disorders. Overall, clinical and experimental data indicate that these drugs are efficacious for a range of diseases, and that the development of drugs with enhanced selectivity for specific VGSC isoforms might be an effective and novel approach for the treatment of several neurological diseases.
电压门控钠离子通道（VGSCs）是内在神经元和肌肉兴奋性的主要调节剂。异常的 VGSC 活性是癫痫发作病理生理学的核心，许多最广泛使用的抗癫痫药物，包括苯妥英、卡马西平和拉莫三嗪，都是 VGSC 功能的抑制剂。这些抗癫痫药物在治疗其他神经系统疾病方面也可能有效，如偏头痛、多发性硬化症、神经退行性疾病和神经性疼痛。在这篇综述中，我们总结了 VGSCs 的结构和功能及其在几种神经疾病病理生理学中的作用。我们还描述了抗癫痫 VGSC 阻滞剂作用机制的生物物理和分子基础，并讨论了这些药物在治疗癫痫和非癫痫疾病方面的疗效。总的来说，临床和实验数据表明，这些药物对一系列疾病有效，并且开发对特定 VGSC 亚型具有更高选择性的药物可能是治疗几种神经疾病的一种有效且新颖的方法。
