Sanon Nathalie T, Gagné Jonathan, Wolf Daniele C, Aboulamer Soumia, Bosoi Ciprian M, Simard Alexe, Messiet Estelle, Desgent Sébastien, Carmant Lionel
Centre de Recherche, Centre Hospitalier Universitaire CHU-Sainte-Justine, Québec, Canada.
Centre de Recherche, Centre Hospitalier Universitaire CHU-Sainte-Justine, Québec, Canada; Département de Sciences Biomédicales, Université de Montréal, Québec, Canada.
Epilepsy Behav. 2018 Feb;79:117-125. doi: 10.1016/j.yebeh.2017.11.019. Epub 2017 Dec 26.
Levetiracetam (LEV), and its newer selective analog brivaracetam (BRV), are two seizure medications that share an innovative mechanism of action targeting the Synaptic Vesicle Protein 2A (SV2A), altering neurotransmitter release and decreasing seizure frequency. Behavioral changes are the most significant adverse effects reported by patients taking LEV. We hypothesize that BRV, the more potent SV2A analog, could exert less behavioral side effects, as it requires lower doses than LEV. Using Kainic Acid (KA)-treated and control rats, we measured adverse behavioral effect profiles of LEV, BRV, or Saline, on social and nonsocial behaviors. Our data indicate that both tested drugs had no effect on locomotion, anxiety levels, fear learning, depression-like behavior, and memory retention in rats. However, when considering social interactions, we first confirmed the epilepsy-induced strong increase in aggressive behaviors and specific hippocampal neuronal loss. We furthermore observed, in Sham rats, that LEV-treated animals were 2 times faster to attack at first encounter, had 5 times more aggressive behaviors, and had significantly less social behaviors than control rats. In all circumstances, BRV rats behaved like Saline rats, suggesting that BRV treatment in rats leads to significantly less aggressive behaviors than LEV treatment at the doses used, while there are limited differential effects between these two drugs on other types of behaviors. Since increased aggressiveness has been reported in patients well controlled on LEV, this study indicates based on our findings, that BRV could represent an effective alternative to LEV to limit aggressiveness problems due to this antiepileptic drug (AED) therapy.
左乙拉西坦（LEV）及其更新的选择性类似物布瓦西坦（BRV）是两种抗癫痫药物，它们具有针对突触囊泡蛋白2A（SV2A）的创新作用机制，可改变神经递质释放并降低癫痫发作频率。行为改变是服用左乙拉西坦的患者报告的最显著不良反应。我们假设，更有效的SV2A类似物布瓦西坦可能产生较少的行为副作用，因为它所需剂量低于左乙拉西坦。我们使用 kainic 酸（KA）处理的大鼠和对照大鼠，测量了左乙拉西坦、布瓦西坦或生理盐水对社交和非社交行为的不良行为影响特征。我们的数据表明，两种受试药物对大鼠的运动、焦虑水平、恐惧学习、抑郁样行为和记忆保持均无影响。然而，在考虑社交互动时，我们首先证实癫痫会导致攻击行为显著增加和特定海马神经元丢失。我们还观察到，在假手术大鼠中，接受左乙拉西坦治疗的动物在首次相遇时攻击速度快2倍，攻击行为多5倍，社交行为明显少于对照大鼠。在所有情况下，布瓦西坦处理的大鼠表现与生理盐水处理的大鼠相似，这表明在所用剂量下，布瓦西坦处理的大鼠比左乙拉西坦处理的大鼠攻击行为显著减少，而这两种药物对其他类型行为的差异作用有限。由于已有报告称接受左乙拉西坦良好控制的患者攻击性增加，基于我们的研究结果，本研究表明，布瓦西坦可能是左乙拉西坦的有效替代品，可减少这种抗癫痫药物（AED）治疗引起的攻击性问题。
