Abstracts

Rationale: Although levetiracetam (LEV, 2S-(oxo-1-pyrrolidinyl)butanamide, Keppra®, UCB Pharma) has been reported to be well tolerated and effective in SE refractory to benzodiazepine (BDZ), there was little preclinical or clinical data concerning the outcomes of LEV in comparison to DZP, and VPA in SE-induced neuronal death. Methods: To address this relevant lack of information, we have performed the preclinical study to investigate the effect of diazepam (DZP), valproate (VPA), and LEV alone, and the efficacy of LEV as an add-on treatment with DZP on the SE-induced neuronal death. Results: In the present study, LEV (≥ 50 mg/kg) was significantly effective to protect neuronal damages from SE in comparison to DZP and VPA. However, it is noticeable that LEV as an add-on drug with DZP could not alleviate SE-induced neuronal damage as compared to LEV alone, and showed the similar effect of DZP alone. VPA (≥ 100 mg/kg) was significantly effective to protect neuronal damages from SE, as compared to DZP. In contrast to LEV, VPA (50 and 100 mg/kg) as an add-on drug with DZP significantly reduced SE-induced neuronal damage as compared to DZP alone, and showed the similar effect of VPA (150 mg/kg) alone. Conclusions: These findings indicate that, unlike VPA, LEV may negatively interact with DZP, and suggest that LEV may be more effective to prevent SE-induced neuronal death as a first line drug than as a second line therapy after BDZ treatment, and that LEV as an add-on drug with BDZ may not provide any additional benefit to outcome of SE.