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

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Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M

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

Lancet Neurol. 2010 Apr;9(4):413-24. doi: 10.1016/S1474-4422(10)70059-4.

PubMed ID

20298965 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Fosphenytoin	Sodium channel protein type 5 subunit alpha	Protein	Humans	Yes	Inhibitor	Details
Phenytoin	Sodium channel protein type 1 subunit alpha	Protein	Humans	Yes	Inhibitor	Details