Retigabine strongly reduces repetitive firing in rat entorhinal cortex

Retigabine (D-23129) [N-(2-amino-3-(4-fluorobenzylamino)phenyl) carbamic ac id ethyl ester] is a novel antiepileptic drug. The compound was shown to po ssess anticonvulsant properties both in vivo and in vitro. We investigated the effects of retigabine on neurones in the rat medial entorhinal cortex u sing conventional intracellular recordings in combined hippocampal-entorhin al cortex slices. Retigabine strongly reduced the number of action potentia ls elicited by 1 s long depolarising current injections. Both the amplitude s of monosynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) and the amplitudes of excitatory postsynaptic potentials (EPSPs) remained unaf fected. The drug increased outward rectification and induced a membrane-pot ential hyperpolarisation in most of the tested neurones. The findings sugge st that retigabine exerts its anticonvulsant effects by activation of a Kconductance, however it cannot be excluded from our experiments that other mechanisms may be involved in the effect of retigabine on membrane properti es. (C) 1999 Elsevier Science B.V. All rights reserved.