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Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy.
Epilepsy Research 1995 November
The anticonvulsant effects of levetiracetam were assessed in two genetic rat models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and tonic-clonic convulsions. In the GAERS model of petit mal epilepsy, levetiracetam markedly suppressed spontaneous spike-and-wave discharge (SWD) but left the underlying EEG trace normal. The effects were already marked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produced no observable effects on behaviour apart from slight reversible sedation at 170 mg/kg. In contrast, piracetam, a structural analogue of levetiracetam, significantly and consistently suppressed SWD in GAERS rats only at the high dose of 1000 mg/kg with some slight effects at lower doses. The effect of piracetam appeared to be due to increased sleeping rather than to a direct antiepileptic effect. The results with levetiracetam argue for a clinical application in both petit mal, absence epilepsy and in treating generalised tonic-clonic and partial seizures.
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