Voltage gated sodium channels as drug discovery targets

• Published in: Channels (Austin, Tex.) Tex.), 2015-11, Vol.9 (6), p.360-366
• Main Authors: Bagal, Sharan K, Marron, Brian E, Owen, Robert M, Storer, R Ian, Swain, Nigel A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analgesics - chemistry; Analgesics - pharmacology; Animals; Anti-Arrhythmia Agents - chemistry; Anti-Arrhythmia Agents - pharmacology; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Drug Discovery - methods; Humans; Molecular Sequence Data; Review; Sodium Channel Blockers - chemistry; Sodium Channel Blockers - pharmacology; sodium channel drugs; sodium channel structure; sodium channel toxins; Voltage-Gated Sodium Channels - metabolism; voltage-gated sodium channels Electrophysiology screening
• ISSN: 1933-6950; 1933-6969
• DOI: 10.1080/19336950.2015.1079674

Voltage-gated sodium (Na V ) channels are a family of transmembrane ion channel proteins. They function by forming a gated, water-filled pore to help establish and control cell membrane potential via control of the flow of ions between the intracellular and the extracellular environments. Blockade of Na V s has been successfully accomplished in the clinic to enable control of pathological firing patterns that occur in a diverse range of conditions such as chronic pain, epilepsy, and cardiac arrhythmias. First generation sodium channel modulator drugs, despite low inherent subtype selectivity, preferentially act on over-excited cells which reduces undesirable side effects in the clinic. However, the limited therapeutic indices observed with the first generation demanded a new generation of sodium channel inhibitors. The structure, function and the state of the art in sodium channel modulator drug discovery are discussed in this chapter.