On the Process of Finding Novel and Selective Sodium Channel Blockers for the Treatment of Diseases

摘要: Blockers of voltage-gated sodium channels have several therapeutic uses, including use as anticonvulsants, antiarrhythmics, and analgesics. However, are challenging drug targets, most the clinically used drugs were found before their channel blocking mechanism was known. Sodium a family ten homologous subtypes, members expressed differentially throughout nervous system in cardiac skeletal muscle tissue. They exist closed, open, inactivated conformational states, selective interactions with one or more these states differentiates therapeutically useful from neurotoxins. Therefore, assays discovery need to be sensitive mechanisms action preferably able distinguish between different states. Electrophysiological ideally suited for this task, recent development automated electrophysiology instrumentation affords medium throughput. Higher capacity amenable studying pharmacology include ligand binding, flux, fluorescent assays.