Ezogabine: development and role in the management of epileptic seizures

Epilepsy which is a diverse set of complex neurological disorders comprised of seizures affecting more than 50 million people worldwide among which 90 % are from developing countries. The aim of current antiepileptic therapy is to control the seizures with minimal side effects and improve the patients' quality of life. Near by about 20 medications are approved by Food and Drug Administration among which only five to six are widely used for the treatment of epileptic seizures. Ezogabine (D-23129) is a recently approved antiepileptic drug approved by USFDA for adjunctive therapy of partial onset seizures. It was developed by Valeant Pharmaceuticals and Glaxosmithkline in 2011 for the management of partial onset seizures. The drug has shown unique mechanism of action among other antiepileptic drugs by facilitating potassium channel current in nerve growth factor differentiated PC12 cells. It also promotes membrane repolarisation and thus opposes rapid repetitive discharges. The drug is quickly absorbed and reaches maximum plasma concentration between 0.5 hour and 2 hours after a single oral dose also showing a moderately high bioavailability, volume of distribution and a terminal half life of 8 to 11 hours. It is metabolized via glucuronidation and acetylation. The various adverse effects found with the drug were related to central nervous system and appeared to be dose related like drowsiness, dizziness, vertigo and confusion etc. All these parameters make it superior from other available drugs for the management of epileptic seizures. The present review describes the development; medicinal chemistry; mechanism of action, pharmacokinetics and pharmacodynamics of Ezogabine. Further the review put forwards the indispensible role of this drug for antiepileptic treatment.