Voltage-Gated Sodium Channels in Drug Discovery

Voltage-gated sodium channels (Nav) control the initiation and propagation of action potential, and thus mediate a broad spectrum of physiological processes, including central and peripheral nervous systems’ function, skeletal muscle contraction, and heart rhythm. Recent advances in elucidating the molecular basis of channelopathies implicating Nav channels are the most appealing druggable targets for pain and many other pathology conditions. This chapter overviews Nav super family from genetic evolution, distribution, human diseases/pathology association, highlighting the most recent structure function breakthrough. The second section will discuss current small and large Nav modulators, including traditional nonselective pore blockers, intracellular modulators, and extracellular modulators.