Margineanu Doru Georg
Department of Neurosciences, Faculty of Medicine and Pharmacy, University of Mons, Ave. Champ de Mars 6, B-7000 Mons, Belgium.
Epilepsy Behav. 2014 Sep;38:131-42. doi: 10.1016/j.yebeh.2013.08.029. Epub 2013 Oct 3.
The number of available anticonvulsant drugs increased in the period spanning over more than a century, amounting to the current panoply of nearly two dozen so-called antiepileptic drugs (AEDs). However, none of them actually prevents/reduces the post-brain insult development of epilepsy in man, and in no less than a third of patients with epilepsy, the seizures are not drug-controlled. Plausibly, the enduring limitation of AEDs' efficacy derives from the insufficient understanding of epileptic pathology. This review pinpoints the unbalanced reductionism of the analytic approaches that overlook the intrinsic complexity of epilepsy and of the drug resistance in epilepsy as the core conceptual flaw hampering the discovery of truly antiepileptogenic drugs. A rising awareness of the complexity of epileptic pathology is, however, brought about by the emergence of nonreductionist systems biology (SB) that considers the networks of interactions underlying the normal organismic functions and of SB-based systems (network) pharmacology that aims to restore pathological networks. By now, the systems pharmacology approaches of AED discovery are fairly meager, but their forthcoming development is both a necessity and a realistic prospect, explored in this review.
在一个多世纪的时间里，可用的抗惊厥药物数量不断增加，目前有近二十多种所谓的抗癫痫药物（AEDs）。然而，它们中没有一种能真正预防/减少人类脑损伤后癫痫的发生，并且不少于三分之一的癫痫患者的癫痫发作无法通过药物控制。很可能，AEDs疗效的长期局限性源于对癫痫病理的理解不足。本综述指出，分析方法存在不平衡的还原论，忽视了癫痫的内在复杂性以及癫痫耐药性，这是阻碍发现真正抗癫痫发生药物的核心概念缺陷。然而，非还原论的系统生物学（SB）的出现，使人们对癫痫病理复杂性的认识不断提高，SB考虑正常机体功能背后的相互作用网络，基于SB的系统（网络）药理学旨在恢复病理网络。目前，AED发现的系统药理学方法相当匮乏，但它们未来的发展既是必要的，也是现实的前景，本综述对此进行了探讨。
