EFFECTS OF LEVETIRACETAM, A NOVEL ANTIEPILEPTIC DRUG, ON CONVULSANT ACTIVITY IN 2 GENETIC RAT MODELS OF EPILEPSY

The anticonvulsant effects of levetiracetam were assessed in two genet ic rat models. In the audiogenic-seizure prone rat, levetiracetam, 5.4 to 96 mg/kg i.p. dose-dependently inhibited both wild running and ton ic-clonic convulsions. In the GAERS model of petit mal epilepsy, levet iracetam markedly suppressed spontaneous spike-and-wave discharge (SWD ) but left.the underlying EEG trace normal. The effects were already m arked at 5.4 mg/kg and did not increase significantly up to 170 mg/kg although more animals were completely protected. Levetiracetam produce d no observable effects on behaviour apart from slight reversible seda tion at 170 mg/kg. In contrast, piracetam, a structural analogue of le vetiracetam, significantly and consistently suppressed SWD in GAERS ra ts only at the high dose of 1000 mg/kg with some slight effects at low er doses. The effect of piracetam appeared to be due to increased slee ping rather than to a direct antiepileptic effect. The results with le vetiracetam argue for a clinical application in both petit mai, absenc e epilepsy and in treating generalised tonic-clonic and partial seizur es.