The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits

Neurosci Lett. 2000 Mar 17;282(1-2):73-6. doi: 10.1016/s0304-3940(00)00866-1.


Retigabine (D-23129) is a novel antiepileptic compound with broad spectrum and potent anticonvulsant properties, both in vitro and in vivo. The compound was shown to activate a K(+) current in neuronal cells. The pharmacology of the induced current displays concordance with the published pharmacology of the M-channel, which recently was correlated to the KCNQ2/3 K(+) channel heteromultimere. We examined the effect of retigabine on KCNQ2/3 expressed in Chinese hamster ovary cells. The compound concentration-dependently activated a K(+) current in transfected cells clamped at -50 mV. The activation was induced by a shift of the opening threshold to more negative potentials. The effect was not mediated by an interaction with the cAMP modulatory site and could be partially blocked by the M-channel antagonist linopirdine. The data display that retigabine is the first described M-channel agonist and support the hypothesis that M-channel agonism is a new mode of action for anticonvulsant drugs. Since the function of this channel is reduced in a hereditary epilepsy syndrome, retigabine may be the first anticonvulsant to directly target the deficit observed in a channelopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • CHO Cells
  • Carbamates / pharmacology*
  • Cricetinae
  • Humans
  • KCNQ2 Potassium Channel
  • KCNQ3 Potassium Channel
  • Patch-Clamp Techniques
  • Phenylenediamines / pharmacology*
  • Potassium Channels / metabolism
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated
  • Transfection


  • Anticonvulsants
  • Carbamates
  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • KCNQ3 Potassium Channel
  • KCNQ3 protein, human
  • Phenylenediamines
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • ezogabine