Abstracts

Brivaracetam (ucb 34714) is a new pyrrolidone derivative, structurally related to levetiracetam (LEV; [italic]Keppra[/italic]^[Ograve]), which displays higher affinity than LEV to the LEV-binding site (the synaptic vesicle protein 2A). We examined its anticonvulsant properties in an animal model of acute, partially drug-resistant self-sustaining status epilepticus (SSSE). SSSE was induced by 30 min intermittent stimulation of the perforant path (PPS) through chronically implanted electrodes in free running adult male Wistar rats. Brivaracetam (0.3-300 mg/kg), vehicle, levetiracetam (2-500 mg/kg), diazepam (10 mg/kg) and brivaracetam/diazepam combinations were injected intravenously 40 min. after onset of PPS. Brivaracetam injected iv during established SSSE, shortened the cumulative duration of active seizures in a dose-dependent manner, to 11% of vehicle-treated controls (20 mg/kg) and 0.8 % of controls (300 mg/kg), compared to 35% of C after levetiracetam (200 mg/kg), 11% of C after seletracetam (300 mg/kg), 15 % of C after diazepam (10 mg/kg) and 1% of C after fosphenytoin (50 mg/kg PE). Brivaracetam, like levetiracetam, potentiated the effect of diazepam: diazepam (1 mg/kg) or brivaracetam (1 mg/Kg) alone had no significant effect, but when combined, they reduced the duration of active seizures to 3% of C. Brivaracetam displayed potent anticonvulsant effects in this animal model of SSSE. However, like all drugs, it required doses much higher for control of established SSSE than those which are effective in animal models of partial and generalized epilepsy. (Supported by VHA, by research grant NS13515 from NINDS, and by a research grant from UCB.)