The therapeutic potential of neuronal K V 7 (KCNQ) channel modulators: an update

Expert Opin Ther Targets. 2008 May;12(5):565-81. doi: 10.1517/14728222.12.5.565.


Background: Neuronal KCNQ channels (K(V)7.2-5) represent attractive targets for the development of therapeutics for chronic and neuropathic pain, migraine, epilepsy and other neuronal hyperexcitability disorders, although there has been only modest progress in translating this potential into useful therapeutics.

Objective: Compelling evidence of the importance of K(V)7 channels as neuronal regulatory elements, readily amenable to pharmacological modulation, has sustained widespread interest in these channels as drug targets. This review will update readers on key aspects of the characterization of these important ion channel targets, and will discuss possible current barriers to their exploitation for CNS therapeutics.

Methods: This article is based on a review of recent literature, with a focus on data pertaining to the roles of these channels in neurophysiology. In addition, I review some of the regulatory elements that influence the channels and how these may relate to channel pharmacology, and present a review of recent advances in neuronal K(V)7 channel pharmacology.

Conclusions: These channels continue to be valid and approachable targets for CNS therapeutics. However, we may need to understand more about the roles of neuronal K(V)7 channels during the development of disease states, as well as to pay more attention to a detailed analysis of the molecular pharmacology of the different channel subfamily members and the modes of interaction of individual modulators, in order to successfully target these channels for therapeutic development.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System Diseases / drug therapy*
  • Controlled Clinical Trials as Topic
  • Drug Delivery Systems*
  • Humans
  • KCNQ Potassium Channels / drug effects*
  • KCNQ Potassium Channels / metabolism
  • KCNQ2 Potassium Channel / drug effects
  • KCNQ2 Potassium Channel / metabolism
  • KCNQ3 Potassium Channel / drug effects
  • KCNQ3 Potassium Channel / metabolism
  • Neurons / metabolism
  • Potassium Channel Blockers / pharmacology


  • KCNQ Potassium Channels
  • KCNQ2 Potassium Channel
  • KCNQ3 Potassium Channel
  • KCNQ5 protein, human
  • Potassium Channel Blockers