Mula Marco
Department of Clinical & Experimental Medicine, Section of Neurology, Amedeo Avogadro University, Corso Mazzini 18, Novara, Italy.
Cent Nerv Syst Agents Med Chem. 2009 Jun;9(2):79-86. doi: 10.2174/187152409788452063.
In the past 20 years, a number of new antiepileptic drugs (AEDs) have been introduced and other molecules are in development, some of which are advantageous in terms of pharmacokinetics, tolerability and potential for drug interactions. These drugs are regarded as second generation compared to older agents such as barbiturates, phenytoin, carbamazepine, ethosuximide and valproic acid. Although some of these second generation compounds may be advantageous in terms of kinetics, tolerability and potential for drug interactions, all of them still target voltage-gated channels or GABA-mediated inhibition, predominantly, without any real improvement in epilepsy therapy. Studies on mechanisms of seizure generation and propagation have identified new potential targets for AEDs. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies. In this review the molecular targets for new AEDs are discussed, providing further suggestions on how future research can be improved.
在过去20年里，多种新型抗癫痫药物（AEDs）已被推出，还有其他一些分子正处于研发阶段，其中一些在药代动力学、耐受性和药物相互作用可能性方面具有优势。与巴比妥类、苯妥英、卡马西平、乙琥胺和丙戊酸等老一代药物相比，这些药物被视为第二代药物。尽管这些第二代化合物中的一些在动力学、耐受性和药物相互作用可能性方面可能具有优势，但它们仍然主要针对电压门控通道或GABA介导的抑制作用，在癫痫治疗方面并没有任何实质性的改善。对癫痫发作产生和传播机制的研究已经确定了AEDs的新潜在靶点。对癫痫病理生理学的日益了解以及分子靶点的结构和功能特征提供了许多创造改进型癫痫治疗方法的机会。在这篇综述中，将讨论新型AEDs的分子靶点，并就如何改进未来研究提供进一步建议。
