Agbo John, Ibrahim Zainab G, Magaji Shehu Y, Mutalub Yahkub Babatunde, Mshelia Philemon Paul, Mhya Daniel H
Department of Clinical Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi, 740272, Nigeria.
Department of Physiology, Faculty of Basic Medical Science, College of Medical Sciences, Abubakar Tafawa Balewa University, Bauchi, 740272, Nigeria.
Acta Epileptol. 2023 Jun 28;5(1):16. doi: 10.1186/s42494-023-00127-2.
Epilepsy is a neurological disease characterized by excessive and abnormal hyper-synchrony of electrical discharges of the brain and a predisposition to generate epileptic seizures resulting in a broad spectrum of neurobiological insults, imposing psychological, cognitive, social and also economic burdens to the sufferer. Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials throughout the central nervous system. Dysfunction of these channels has been implicated in the pathogenesis of epilepsy. VGSC inhibitors have been demonstrated to act as anticonvulsants to suppress the abnormal neuronal firing underlying epileptic seizures, and are used for the management and treatment of both genetic-idiopathic and acquired epilepsies. We discuss the forms of idiopathic and acquired epilepsies caused by VGSC mutations and the therapeutic efficacy of VGSC blockers in idiopathic, acquired and pharmacoresistant forms of epilepsy in this review. We conclude that there is a need for better alternative therapies that can be used alone or in combination with VGSC inhibitors in the management of epilepsies. The current anti-seizure medications (ASMs) especially for pharmacoresistant epilepsies and some other types of epilepsy have not yielded expected therapeutic efficacy partly because they do not show subtype-selectivity in blocking sodium channels while also bringing side effects. Therefore, there is a need to develop novel drug cocktails with enhanced selectivity for specific VGSC isoforms, to achieve better treatment of pharmacoresistant epilepsies and other types of epileptic seizures.
癫痫是一种神经系统疾病，其特征为大脑电活动过度且异常的高度同步化，以及易引发癫痫发作，从而导致广泛的神经生物学损伤，给患者带来心理、认知、社会和经济负担。电压门控钠通道（VGSCs）对于整个中枢神经系统动作电位的产生和传播至关重要。这些通道的功能障碍与癫痫的发病机制有关。已证明VGSC抑制剂可作为抗惊厥药，抑制癫痫发作背后的异常神经元放电，并用于治疗遗传性特发性癫痫和获得性癫痫。在本综述中，我们讨论了由VGSC突变引起的特发性和获得性癫痫的形式，以及VGSC阻滞剂在特发性、获得性和药物难治性癫痫形式中的治疗效果。我们得出结论，需要更好的替代疗法，可单独使用或与VGSC抑制剂联合用于癫痫的治疗。目前的抗癫痫药物（ASMs），特别是用于药物难治性癫痫和其他一些类型癫痫的药物，尚未产生预期的治疗效果，部分原因是它们在阻断钠通道时不显示亚型选择性，同时还会带来副作用。因此，需要开发对特定VGSC亚型具有更高选择性的新型药物组合，以更好地治疗药物难治性癫痫和其他类型的癫痫发作。
