KCNQ potassium channels: drug targets for the treatment of epilepsy and pain

Abstract

Epilepsy and neuropathic pain are disorders characterised by excessive neuronal activity. These disorders are currently managed by drugs that are capable of dampening neuronal excitability, including voltage-gated sodium channel blockers, voltage-operated calcium channel modulators and modulators of inhibitory GABAergic neurotransmission. However, these drugs are rarely 100% efficacious and their use is often associated with limiting side effects. Thus, there is a clear medical need for novel agents to treat these diseases. One potential mechanism that has not yet been exploited is potassium (K⁺) channel opening. A significant (and growing) body of genetic, molecular, physiological and pharmacological evidence now exists to indicate that KCNQ-based currents represent particularly interesting targets for the treatment of diseases such as epilepsy and neuropathic pain. Evidence supporting these K⁺ channels as novel drug targets will be reviewed in the following article. Worldwide patent activity relating to KCNQ channels and KCNQ-modulating drugs and their uses will also be summarised.

• epilepsy
• KCNQ2
• KCNQ3
• pain
• potassium channel