Rundfeldt C
Department of Pharmacology, Arzneimittelwerk Dresden GmbH, Corporate R & D, Radebeul, Germany.
Eur J Pharmacol. 1997 Oct 8;336(2-3):243-9. doi: 10.1016/s0014-2999(97)01249-1.
The patch-clamp technique was used to measure currents passing through K+ channels in neuronal cell preparations. Retigabine (D-23129, N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester) activated a K+ conductance in slightly depolarized NG108-15 neuronal cells in a dose-dependent manner (0.1-10 microM). At the K+ reversal potential, no current could be elicited and in hyperpolarized cells the current was reversed. A similar current was elicited in primary cultures of mouse cortical neurones and in differentiated hNT cells, a cell line derived from human neuronal cells. At higher concentrations, retigabine also partially blocked voltage activated K+ currents. None of the tested anticonvulsants, phenytoin, carbamazepine and valproate and none of the K+ channel openers cromakalim, diazoxide and pinacidil exerted a similar effect. The current was not affected by the K+ channel blocker glibenclamide (10 microM) but was fully blocked by application of Ba2+ (10.8 mM). Exchange of K+ with cesium in the intracellular space also fully abolished the current. It can be expected that the K+ channel opening effect contributes to the anticonvulsant activity of retigabine.
