Effects of retigabine on rhythmic synchronous activity of human neocortical slices

Abstract

The antiepileptic effects of the novel antiepileptic drug retigabine (D-23129) [ N-(2-amino-4-(4-flurobenzylamino)phenyl) carbamid acid ethyl ester] were tested in neocortical slice preparations ( n=23) from 17 patients (age, 3–42 years) who underwent surgery for the treatment of intractable epilepsy. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves, as well as of epileptiform field potentials (EFP) elicited by superfusion with Mg 2+-free solution without or with addition of 10 μmol/l bicuculline. (1) Spontaneous rhythmic sharp waves ( n=6), with retigabine application, the repetition rate was decreased down to 12–47% of initial value (10 μmol/l, n=3) after 180 min or suppressed completely within 12 min (50 μmol/l, n=3). (2) Low Mg 2+ EFP ( n=9), with retigabine application, the repetition rate was decreased down to 50 and 65% of initial value (10 μmol/l; n=2) after 180 min or suppressed completely after 9–55 min (10, 50 and 100 μmol/l; n=2 in each case). In one slice only a transient reduction of the repetition rate was seen with 10 μmol/l retigabine. (3) Low Mg 2+ EFP with addition of bicuculline ( n=8), with retigabine application, the repetition rate was decreased down to 12–55% of initial value (10 μmol/l; n=4) after 180 min or suppressed completely after 6–30 min (50 and 100 μmol/l; n=2 in each case). The depressive effect of retigabine was reversible in all but one slice. The results show a clear antiepileptic effect of retigabine in human neocortical slices on spontaneously occurring rhythmic sharp waves and different types of induced seizure activity.