Gabapentin-lactam, a close analogue of the anticonvulsant gabapentin, exerts convulsant activity in amygdala kindled rats

The cyclic GABA analogue gabapentin (GBP), which recently has been marketed for treatment of epilepsy, is particularly effective against complex-parti al seizures as occurring in temporal lobe epilepsy. In the present study, w e compared the effects of GBP and its lactam analogue (GBP-L) in the amygda la kindling model of temporal lobe epilepsy. In fully kindled rats, GBP (50 mg/kg and 100 mg/kg i.p.) dose-dependently increased the threshold for foc al seizures and inhibited the progression from focal to generalized seizure s. This effect was not associated with any marked adverse effects. In contr ast, GBP-L (10-50 mg/kg) induced myoclonic activity and generalized clonic seizures in kindled rats, demonstrating a striking qualitative difference b etween the two compounds. By comparison with non-kindled rats it was shown that kindling markedly enhanced the sensitivity of rats to the convulsant a ctivity of GBP-L. The finding that the anticonvulsant efficacy of GBP is lo st by lactam formation indicates that GBP and GBP-L differ in their mechani sm(s) of action.