Potassium channel enhancers to treat pain and epilepsy

Epilepsy and pain are both disorders involving neuronal hyperexcitability. Treatments for both epilepsy and pain have mostly focused on reducing excitability by inhibiting voltage-dependent sodium channels, as exemplified by carbamazepine, phenytoin, and lacosamide used to treat epilepsy and VX-548 to treat pain. An alternative approach is to exploit our growing knowledge about the differential expression of different kinds of potassium channels in different neuronal types to selectively inhibit excitability of specific neuronal types by enhancing voltage-dependent potassium channels. We have identified specific members families of potassium channels as promising targets for inhibiting pain-sensing neurons to treat pain and neocortical excitatory neurons to treat epilepsy. Small scale screens have resulted in hits for enhancers of potassium channels. We will expand the screens to other targets and use the hits as tool compounds to determine which channels are most promising as novel drug development targets.