Ezogabine: A New Angle on Potassium Gates

Abstract

Ezogabine is a new drug for adjunctive therapy of partial-onset seizures with a novel mechanism of action. As a potassium-channel facilitator, it promotes membrane repolarization and thus opposes rapid repetitive discharges. Side effects are typical for antiepileptic drugs and the safety profile is good. Occasional instances of urinary difficulty may require surveillance.

Ezogabine for the Adjunctive Treatment of Partial Onset Seizures in Adults with Epilepsy

“…In general, side-effects and efficacy seem to be best balanced at a dose of 300 mg given three times daily, however, doses up to 1200 mg have been used in clinical trials. 9 Rapid, forced titration of the medication is associated with frequent CNS-related adverse events, though the majority of these events tend to be mild to moderate in nature. Slow titration is likely to result in better drug tolerance and fewer treatment withdrawals.…”

“…7,9 In other words, ezogabine binding ultimately results in the need for a smaller depolarizing shift to open the channel, an increase in the speed at which the channel opens, and a prolongation of the open state of the channel (up to 4-fold). 16 Taken together, these effects result in an inhibition of repetitive firing.…”

“…Mutations of the genes corresponding to these channels, KCNQ2 and KCNQ3, have been identified as associated with benign familial convulsions and other idiopathic types of epilepsy. [9][10][11][12][13] This family of channels is associated with the outward K + current that causes repolarization of the membrane post action potential, also known as the M-current. 9 Patients are susceptible to epileptic activity when this current is inhibited.…”

“…[9][10][11][12][13] This family of channels is associated with the outward K + current that causes repolarization of the membrane post action potential, also known as the M-current. 9 Patients are susceptible to epileptic activity when this current is inhibited. Ezogabine is believed to exert its primary anti-seizure effect by enhancing the M-current.…”

“…The drug has not been shown to affect K + channels located in cardiac tissue (Kv7.1 channels coded by gene KCNQ1), as the glycine target needed for ezogabine binding is absent. 9 However, there is an overlap of K + channel types located in the CNS and in the urothelium of the bladder. 28 An analysis of 1365 subjects exposed to ezogabine revealed voiding difficulties in 8.6%, with an additional 3% reporting slight increases in post-void residual volume (PVR).…”