Effects of retigabine on rhythmic synchronous activity of human neocortical slices

The antiepileptic effects of the novel antiepileptic,drug retigabine (D-231 29) [N-(2-amino-4-(4-flurobenzylamino)phenyl) carbamid acid ethyl ester] we re tested in neocortical slice preparations (n = 23) from 17 patients (age, 3-42 years) who underwent surgery for the treatment of intractable epileps y. Epileptiform events consisted of spontaneously occurring rhythmic sharp waves, as well as of epileptiform field potentials (EFP) elicited by superf usion with Mg2+-free solution without or with addition of 10 mu mol/l bicuc ulline. (1) Spontaneous rhythmic sharp waves (n = 6), with retigabine appli cation, the repetition rate was decreased down to 12-47% of initial value ( 10 mu mol/l, n = 3) after 180 min or suppressed completely within 12 min (5 0 mu mol/l, n = 3). (2) Low Mg2+ EFP (n = 9), with retigabine application, the repetition rate was decreased down to 50 and 65% of initial value (10 m u mol/l; n = 2) after 180 min or suppressed completely after 9-55 min (10, 50 and 100 mu mol/l; n = 2 in each case). In one slice only a transient red uction of the repetition rate was seen with 10 mu mol/l retigabine. (3) Low Mg2+ EFP with addition of bicuculline (n = 8), with retigabine application , the repetition rate was decreased down to 12-55% of initial value (10 mu mol/l; n = 4) after 180 min or suppressed completely after 6-30 min (50 and 100 mu mol/l; n = 2 in each case). The depressive effect of retigabine was reversible in all but one slice. The results show a Clear antiepileptic ef fect of retigabine in human neocortical slices on spontaneously occurring r hythmic sharp waves and different types of induced seizure activity. (C) 20 01 Elsevier Science B.V. All rights reserved.