Institute of Drug Research, School of Pharmacy, Faculty of Medicine, and the David R. Bloom Centre for Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997.
Since the early 1990s, many new antiepileptic drugs (AEDs) that offer appreciable advantages in terms of their favourable pharmacokinetics, improved tolerability and lower potential for drug-drug interactions have entered the market. However, despite the therapeutic arsenal of old and new AEDs, approximately 30% of patients with epilepsy still suffer from seizures. Thus, there remains a substantial need for the development of more efficacious AEDs for patients with refractory seizures. Here, we briefly review the emerging knowledge on the pathological basis of epilepsy and how it might best be used in the design of new therapeutics. We also discuss the current approach to AED discovery and highlight some of the unique features of newer models of pharmacoresistance and epileptogenesis that have emerged in recent years.
自 20 世纪 90 年代初以来，许多具有良好药代动力学特性、更高耐受性和更低药物相互作用潜力的新型抗癫痫药物（AED）已进入市场。然而，尽管有新旧 AED 的治疗武器库，大约 30%的癫痫患者仍然遭受癫痫发作。因此，对于难治性癫痫发作的患者来说，仍然需要开发更有效的 AED。在这里，我们简要回顾一下癫痫的病理基础的新知识，以及如何最好地将其应用于新疗法的设计。我们还讨论了目前的 AED 发现方法，并强调了近年来出现的一些新型抗药性和癫痫发生模型的独特特征。
