Anticonvulsant effects of lamotrigine, a novel antiepileptic drug, on amygdaloid and hippocampal kindled seizures in rats

Lamotrigine is a novel antiepileptic drug that is effective in partial seizures and generalized seizures. We examined the effects of lamotrigine on amygdaloid or hippocampal kindles seizures in rats. The results are: (1) lamotrigine administration (13.4 mg/kg i.p.) 2, 6 and 24 hours prior to kindling stimulation significantly suppressed both seizures and after discharge durations of kindled seizures. (2) The anticonvulsant effect of lamotrigine was in a dose-dependent manner. The highest dose (13.4 mg/kg i.p.) of lamotrigine in the present study completely abolished amygdaloid kindled seizures. (3) The effect of lamotrigine on seizures gradually decreased as the stimulus intensity was increased up to three times of GST (generalized seizure threshold), suggesting that the mechanism of the effect is associated with elevation of seizure triggering threshold. (4) None of the doses of lamotrigine induced any behavioral side effects. These results indicate that lamotrigine is a potent anticonvulsant against kindled seizures. Absence of obvious side effects could provide clinical usefulness to lamotrigine as an antiepileptic agent.