Meldrum B S
Department of Neurology, University of London, England.
Epilepsia. 1996;37 Suppl 6:S4-11. doi: 10.1111/j.1528-1157.1996.tb06038.x.
Novel antiepileptic drugs (AEDs) are thought to act on voltage-sensitive ion channels, on inhibitory neurotransmission or on excitatory neurotransmission. Two successful examples of rational AED design that potentiate GABA-mediated inhibition are vigabatrin (VGB) by irreversible inhibition of GABA-transaminase, and tiagabine (TGB) by blocking GABA uptake. Lamotrigine (LTG) prolongs inactivation of voltage-dependent sodium channels. The anticonvulsant action of remacemide (RCM) is probably largely due to blockade of NMDA receptors and prolonged inactivation of sodium channels induced by its desglycinated metabolite. Felbamate (FBM) apparently blocks NMDA receptors, potentiates GABA-mediated responses, blocks L-type calcium channels, and possibly also prolongs sodium channel inactivation. Similarly, topiramate (TPM) has multiple probable sites of action, including sodium channels, GABA receptors, and glutamate (AMPA) receptors. Gabapentin (GBP) apparently has a completely novel type of action, probably involving potentiation of GABA-mediated inhibition and possibly also inactivation of sodium channels. The therapeutic advantages of the novel AEDs are as yet only partially explained by our present understanding of their mechanisms of action.
新型抗癫痫药物（AEDs）被认为作用于电压敏感性离子通道、抑制性神经传递或兴奋性神经传递。合理设计的AEDs增强GABA介导的抑制作用的两个成功例子是，通过不可逆抑制GABA转氨酶的氨己烯酸（VGB），以及通过阻断GABA摄取的替加宾（TGB）。拉莫三嗪（LTG）延长电压依赖性钠通道的失活。瑞玛西胺（RCM）的抗惊厥作用可能主要归因于其对NMDA受体的阻断以及由其去甘氨酸代谢产物诱导的钠通道的延长失活。非氨酯（FBM）明显阻断NMDA受体，增强GABA介导的反应，阻断L型钙通道，并且可能还延长钠通道失活。同样，托吡酯（TPM）有多个可能的作用位点，包括钠通道、GABA受体和谷氨酸（AMPA）受体。加巴喷丁（GBP）显然有一种全新的作用类型，可能涉及增强GABA介导的抑制作用，并且也可能使钠通道失活。目前我们对新型AEDs作用机制的理解仅部分解释了它们的治疗优势。
