Kälviäinen R, Keränen T, Riekkinen P J
Department of Neurology, University of Kuopio, Finland.
Drugs. 1993 Dec;46(6):1009-24. doi: 10.2165/00003495-199346060-00006.
There are several new antiepileptic drugs undergoing extensive clinical investigation. Five new drugs--vigabatrin, lamotrigine, gabapentin, felbamate and oxcarbazepine--appear to be the most widely tested and promising agents. Vigabatrin is most effective in drug-resistant partial epilepsy. Vigabatrin is also effective in infantile spasms, but seems to have negative effects on myoclonic epilepsies and absence seizures. Lamotrigine and felbamate seem to be effective in partial epilepsy and in Lennox-Gastaut syndrome. In addition, lamotrigine and felbamate seem to have efficacy in idiopathic generalised epilepsies. Oxcarbazepine appears to be equally as effective as carbamazepine, but less toxic. Gabapentin has few adverse effects and has efficacy in some patients with drug-resistant partial epilepsy. Some of the new antiepileptic drugs modify excitatory or inhibitory amino acid transmission, but some of them may employ new, still unknown mechanisms of action. Depending on the mechanism of action, the therapeutic effectiveness of the antiepileptic drugs may differ in specific epileptic syndromes. Future antiepileptic drugs may thus give us the possibility to design rational polypharmacy for individual patients by combining agents with different spectra of effectiveness. Considering the goal of good tolerability in the development of the new antiepileptic drugs, polypharmacy with these agents is not expected to increase adverse effects significantly.
有几种新型抗癫痫药物正在进行广泛的临床研究。五种新药——氨己烯酸、拉莫三嗪、加巴喷丁、非氨酯和奥卡西平——似乎是接受测试最广泛且最有前景的药物。氨己烯酸对耐药性部分性癫痫最为有效。氨己烯酸对婴儿痉挛症也有效,但似乎对肌阵挛性癫痫和失神发作有负面影响。拉莫三嗪和非氨酯似乎对部分性癫痫和伦诺克斯 - 加斯托综合征有效。此外,拉莫三嗪和非氨酯似乎对特发性全身性癫痫也有效。奥卡西平似乎与卡马西平疗效相当,但毒性较小。加巴喷丁不良反应少,对一些耐药性部分性癫痫患者有效。一些新型抗癫痫药物可改变兴奋性或抑制性氨基酸传递,但其中一些可能采用新的、尚不清楚的作用机制。根据作用机制,抗癫痫药物在特定癫痫综合征中的治疗效果可能不同。因此,未来的抗癫痫药物可能使我们有机会通过联合使用具有不同疗效谱的药物,为个体患者设计合理的联合用药方案。考虑到新型抗癫痫药物研发中良好耐受性的目标,这些药物的联合使用预计不会显著增加不良反应。