White H Steve, Smith Misty D, Wilcox Karen S
Anticonvulsant Drug Development Program, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84108, USA.
Int Rev Neurobiol. 2007;81:85-110. doi: 10.1016/S0074-7742(06)81006-8.
The management of seizures in the patient with epilepsy relies heavily on antiepileptic drug (AED) therapy. Fortunately, for a large percentage of patients, AEDs provide excellent seizure control at doses that do not adversely affect normal function. At the molecular level, the majority of AEDs are thought to modify excitatory and inhibitory neurotransmission through effects on voltage-gated ion channels (e.g., sodium and calcium) and gamma-aminobutyric acid (GABA)(A) receptors, respectively. In addition to these effects, two of the "second-generation" AEDs have been found to limit glutamate-mediated excitatory neurotransmission (i.e., felbamate and topiramate). Not surprisingly, those AEDs with broad spectrum clinical activity are often found to exert an action at more than one molecular target. Emerging evidence suggests that receptor and voltage-gated subunits are modified by chronic seizures. Thus, attempts to understand the relationship between target and effect continue to provide important information about the neuropathology of the epileptic network and to facilitate the development of novel therapies for the treatment of refractory epilepsy.
癫痫患者的癫痫发作管理在很大程度上依赖于抗癫痫药物（AED）治疗。幸运的是，对于很大一部分患者来说，AEDs在不影响正常功能的剂量下就能很好地控制癫痫发作。在分子水平上，大多数AEDs被认为分别通过对电压门控离子通道（如钠通道和钙通道）和γ-氨基丁酸（GABA）（A）受体的作用来改变兴奋性和抑制性神经传递。除了这些作用外，还发现两种“第二代”AEDs能限制谷氨酸介导的兴奋性神经传递（即非氨酯和托吡酯）。不出所料，那些具有广谱临床活性的AEDs往往被发现作用于多个分子靶点。新出现的证据表明，慢性癫痫发作会改变受体和电压门控亚基。因此，试图理解靶点与效应之间的关系继续为癫痫网络的神经病理学提供重要信息，并促进难治性癫痫新疗法的开发。
