Retigabine strongly reduces repetitive firing in rat entorhinal cortex

Retigabine (D-23129) [N-(2-amino-3-(4-fluorobenzylamino)phenyl) carbamic acid ethyl ester] is a novel antiepileptic drug. The compound was shown to possess anticonvulsant properties both in vivo and in vitro. We investigated the effects of retigabine on neurones in the rat medial entorhinal cortex using conventional intracellular recordings in combined hippocampal-entorhinal cortex slices. Retigabine strongly reduced the number of action potentials elicited by 1 s long depolarising current injections. Both the amplitudes of monosynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) and the amplitudes of excitatory postsynaptic potentials (EPSPs) remained unaffected. The drug increased outward rectification and induced a membrane-potential hyperpolarisation in most of the tested neurones. The findings suggest that retigabine exerts its anticonvulsant effects by activation of a K+ conductance, however it cannot be excluded from our experiments that other mechanisms may be involved in the effect of retigabine on membrane properties. (C) 1999 Elsevier Science B.V. All rights reserved.