Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders

Voltage-gated sodium channels (VGSCs) are key mediators of intrinsic neuronal and muscle excitability. AbnormalVGSC activity is central to the pathophysiology of epileptic seizures, and many of the most widely used antiepilepticdrugs, including phenytoin, carbamazepine, and lamotrigine, are in hibitors of VGSC function. These antiepilepticdrugs might also be effi cacious in the treatment of other nervous system disorders, such as migraine, multiplesclerosis, neurodegenerative diseases, and neuropathic pain. In this Review, we summarise the structure and functionof VGSCs and their involvement in the pathophysiology of several neurological disorders. We also describe thebiophysical and molecular bases for the mechanisms of action of antiepileptic VGSC blockers and discuss the effi cacyof these drugs in the treat ment of epileptic and non-epileptic disorders. Overall, clinical and experimental data indicatethat these drugs are effi cacious for a range of diseases, and that the development of drugs with enhanced selectivity forspecifi c VGSC isoforms might be an eff ective and novel approach for the treatment of several neurological diseases.