Exploring the latest avenues for antiepileptic drug discovery and development
Exploring the latest avenues for antiepileptic drug discovery and development
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DOI：
10.1517/17460441.2016.1154840
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发表时间：
2016-03
影响因子：
6.3
通讯作者：
K. Łukawski;Paweł Gryta;J. Łuszczki;S. Czuczwar
中科院分区：
文献类型：
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作者：
K. Łukawski;Paweł Gryta;J. Łuszczki;S. Czuczwar
摘要简介：在约30%的癫痫患者中，现有的抗癫痫药物不能充分控制癫痫的发作。需要更新的药物，不仅旨在抑制癫痫发作活动，而且有效地抑制癫痫的发生。涵盖的领域：在这篇综述中，作者考虑了不同的治疗耐药癫痫的方法，以及如何阻止癫痫发生的各种可能的方法。专家观点：抗癫痫药物抗癫痫作用的证据有限癫痫持续状态后的动物模型可能有助于在已经批准的非抗癫痫药物或其他药物中发现抗癫痫化合物。一个很好的例子是氯沙坦，它在体内显著抑制癫痫的发生。一些影响mTOR信号系统的药物，或抑制致痫细胞因子和植物来源的细胞因子(白藜芦醇)的合成的药物在这方面似乎也是有效的。此外，过氧化体增殖物激活受体激动剂已被证明在某些癫痫模型中有效，但关于其可能的抗癫痫活性的数据相当有限。除了发现新的抗癫痫和/或抗癫痫化合物外，还有可能通过合理使用抗癫痫药物组合来改善耐药病例的治疗。
ABSTRACT Introduction: In about 30% of patients with epilepsy, seizures are not sufficiently controlled with the available antiepileptic medication. There is a need for newer drugs, not only aimed at suppressing seizure activity but for the efficient inhibition of epileptogenesis. Areas covered: In this review, the authors consider different approaches for the management of drug-resistant epilepsy and various possible ways on how to stop epileptogenesis. Expert opinion: There is limited evidence for antiepileptogenic effects of antiepileptic drugs. Post-status epilepticus animal models will probably help the discovery of antiepileptogenic compounds among already approved non-antiepileptic drugs or other agents. A good example is losartan, which significantly inhibits epileptogenesis in vivo. Some agents that affect the mTOR signaling system, or that inhibit the synthesis of the proconvulsant cytokine as well as those derived from plants (resveratrol) also seem effective in this regard. Furthermore, agonists of peroxisome proliferator-activated receptors have proven effective in some models of seizures but data on their possible antiepileptogenic activity is quite limited. In addition to the discovery of new antiepileptogenic and/or antiepileptic compounds, there is a possibility of improving the treatment of drug-resistant cases through the rational use of antiepileptic drug combinations.