Physiology Department, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Department of Neurology, Division of Neurosurgery, Hospital das Clínicas, University of São Paulo, São Paulo, SP, Brazil.
Seizure. 2021 Aug;90:99-109. doi: 10.1016/j.seizure.2021.02.031. Epub 2021 Mar 3.
The basic mechanisms by which brain insults, such as trauma, stroke or status epilepticus produce epilepsy are not completely understood, and effective preventive measures and treatment are still not available in the clinical setting. Over the last 2 decades we have conducted several studies with animal models of epilepsy (rodents and non-human primates) and demonstrated that drugs that modify neuronal plastic processes, such as anticholinergic agents (e.g., antimuscarinic compounds), if administered soon after brain injury and over a period of 10-20 days, have the potential to modify the natural course of post-traumatic epilepsy. To that end treatment with scopolamine showed promising results as a candidate agent in both the pilocarpine and kainate models. We then showed that biperiden, yet another cholinergic antagonist acting in the muscarinic receptor, that is widely used to treat Parkinson's disease, also decreased the incidence and intensity of spontaneous epileptic seizures, delaying their appearance in the pilocarpine model of epilepsy. In other words, biperiden showed to be a potential candidate to be further investigated as an antiepileptogenic agent. Accordingly, we tested the safety of biperiden in a small group of patients (as a small phase II safety assessment) and confirmed its safety in the context of traumatic brain injury (TBI). Now, we provide information on our ongoing project to evaluate the efficacy of biperiden in preventing the development of epilepsy in patients that suffered TBI, in a double blind, randomized, placebo-controlled trial.
脑损伤（如创伤、中风或癫痫持续状态）导致癫痫的基本机制尚未完全阐明，临床上仍缺乏有效的预防措施和治疗方法。在过去的 20 年中，我们用癫痫动物模型（啮齿动物和非人灵长类动物）进行了几项研究，证明了可以改变神经元可塑性过程的药物，如抗胆碱能药物（如抗毒蕈碱化合物），如果在脑损伤后不久和 10-20 天的时间内给药，有潜力改变创伤后癫痫的自然病程。为此，东莨菪碱治疗在匹罗卡品和海人酸模型中显示出作为候选药物的有希望的结果。然后我们表明，另一种作用于毒蕈碱受体的胆碱能拮抗剂——比哌立登，广泛用于治疗帕金森病，也降低了自发性癫痫发作的发生率和强度，延缓了它们在匹罗卡品癫痫模型中的出现。换句话说，比哌立登被证明是一种有潜力的候选药物，可以进一步作为抗癫痫发生剂进行研究。因此，我们在一小群患者中测试了比哌立登的安全性（作为小型 II 期安全性评估），并在创伤性脑损伤（TBI）的背景下证实了其安全性。现在，我们提供了有关我们正在进行的项目的信息，该项目旨在评估比哌立登在预防 TBI 患者癫痫发作中的疗效，这是一项双盲、随机、安慰剂对照试验。
