The preclinical discovery and development of ezogabine for the treatment of epilepsy

Expert Opin Drug Discov. 2013 Nov;8(11):1429-37. doi: 10.1517/17460441.2013.837882. Epub 2013 Sep 21.


Introduction: The weak anticonvulsant activity of the analgesic flupirtine led to the creation of ezogabine; an analogue which demonstrated both stronger antiepileptic activity and weaker analgesic effects. It's use as an anticonvulsant has been particularly effective in treating patients who have therapy-resistant epilepsy. Ezogabine binds to the KCNQ potassium channel, thereby decreasing the membrane potential threshold for its activation and increasing the probability of its maximum opening.

Areas covered: This drug discovery case history provides an overview of the history of the anticonvulsant, ezogabine, and presents relevant information pertaining to its discovery and preclinical development. The article helps explain the methods of discovery through the explanation of ezogabine's mechanism of action. Further, the authors also highlight the drugs clinical development and its postlaunch developments.

Expert opinion: More intense investment in research on the molecular mechanism of action early in the preclinical development of a drug could allow for the more suitable planning of preclinical studies and for the early discovery of specific, but important drug toxicities. This investment would make transitioning from the preclinical to the clinical phase easier and could result in better planning for what will be more productive clinical studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use*
  • Carbamates / pharmacology*
  • Carbamates / therapeutic use*
  • Drug Discovery*
  • Epilepsy / drug therapy*
  • Humans
  • Phenylenediamines / pharmacology*
  • Phenylenediamines / therapeutic use*
  • Product Surveillance, Postmarketing


  • Anticonvulsants
  • Carbamates
  • Phenylenediamines
  • ezogabine