UCB Pharma S.A., CNS Research, Chemin du Foriest, B-1420 Braine-l'Alleud, Belgium.
Epilepsy Res. 2010 Sep;91(1):74-83. doi: 10.1016/j.eplepsyres.2010.06.014. Epub 2010 Aug 1.
Several antiepileptic drugs (AEDs) may induce memory deficits when tested in preclinical models at doses that exert significant protection against seizures. Brivaracetam (BRV) is a novel high-affinity SV2A ligand also displaying inhibitory activity at neuronal voltage-gated sodium channels. In the present study we have investigated the effects of BRV, at doses that exerted marked anticonvulsant effects in kindled rats, upon cognitive functioning and memory in both normal and amygdala-kindled rats using place learning version of Morris water maze. In addition the effect of BRV on long-term potentiation (LTP) in rat hippocampal slices has been investigated. BRV (2.1, 6.8 or 21.0mg/kg i.p.) was injected daily, 60min before each session. Results indicated that in both normal and amygdala-kindled rats BRV did not alter the latency to find the hidden platform or swimming speed during the four consecutive days of learning. Similarly, the time spent in the target quadrant, used as a further independent index of spatial memory, was not modified by BRV treatment. Likewise, BRV did not affect the LTP induction in CA1 hippocampal region when tested at 3-30microM concentration range, which had been demonstrated to significantly reduce epileptiform activity in slice models. Based on the results of the present study it can be expected that BRV will not have detrimental effects on hippocampal-dependent cognitive functions in patients with epilepsy.
几种抗癫痫药物（AEDs）在临床前模型中以能够显著预防癫痫发作的剂量测试时，可能会引起记忆缺陷。布瓦雷西坦（BRV）是一种新型高亲和力 SV2A 配体，在神经元电压门控钠离子通道上也具有抑制活性。在本研究中，我们研究了 BRV 在点燃大鼠中发挥明显抗惊厥作用的剂量对正常和杏仁核点燃大鼠认知功能和记忆的影响，使用 Morris 水迷宫的位置学习版本。此外，还研究了 BRV 对大鼠海马切片长时程增强（LTP）的影响。BRV（2.1、6.8 或 21.0mg/kg 腹腔注射）每天注射一次，在每次给药前 60 分钟。结果表明，在正常和杏仁核点燃的大鼠中，BRV 不会改变寻找隐藏平台的潜伏期或在学习的连续四天中的游泳速度。同样，BRV 处理也不会改变作为空间记忆的另一个独立指标的目标象限中的时间。同样，当在 3-30μM 浓度范围内测试时，BRV 也不会影响 CA1 海马区的 LTP 诱导，因为它已被证明可显著减少切片模型中的癫痫样活动。基于本研究的结果，可以预期 BRV 不会对癫痫患者的海马依赖认知功能产生不利影响。
