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-partial seizures as occurring in temporal lobe epilepsy. In the present study, we compared the effects of GBP and its lactam analogue (GBP-L) in the amygdala 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 focal seizures and inhibited the progression from focal to generalized seizures. This effect was not associated with any marked adverse effects. In contrast, GBP-L (10-50 mg/kg) induced myoclonic activity and generalized clonic seizures in kindled rats, demonstrating a striking qualitative difference between the two compounds. By comparison with non-kindled rats it was shown that kindling markedly enhanced the sensitivity of rats to the convulsant activity of GBP-L. The finding that the anticonvulsant efficacy of GBP is lost by lactam formation indicates that GBP and GBP-L differ in their mechanism(s) of action.