Silver J M, Shin C, McNamara J O
Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC.
Ann Neurol. 1991 Apr;29(4):356-63. doi: 10.1002/ana.410290404.
We sought to determine whether the clinically effective anticonvulsant drug valproate exhibited antiepileptogenic properties in the kindling model (we use the term anticonvulsant to mean suppression of seizure, and antiepileptogenic to mean suppression of development of epilepsy). We compared and contrasted valproate with two other anticonvulsant drugs, phenobarbital and carbamazepine. We investigated the effects of these drugs on the development of kindling, that is, the number of stimulation-induced afterdischarges required to induce enhanced seizure susceptibility in rats. Valproate exhibited powerful antiepileptogenic effects as evident in a dose-dependent increase in the number of afterdischarges required to induce kindling. These effects were not due to retained valproate or an active metabolite merely masking the expression of kindled seizures. By contrast, carbamazepine was devoid of any antiepieptogenic effects despite exhibiting marked anticonvulsant effects. Like valproate, phenobarbital exhibited both antiepileptogenic and anticonvulsant properties, but its antiepileptogenic properties were significantly less pronounced. The antiepileptogenic effects of valproate and phenobarbital strengthen the candidacy of these agents for the clinical studies needed to investigate pharmacological prevention of the development of epilepsy in high-risk groups.
我们试图确定临床上有效的抗惊厥药物丙戊酸盐在点燃模型中是否具有抗癫痫发生的特性（我们使用“抗惊厥”一词表示抑制癫痫发作，“抗癫痫发生”表示抑制癫痫的发展）。我们将丙戊酸盐与另外两种抗惊厥药物苯巴比妥和卡马西平进行了比较和对比。我们研究了这些药物对点燃发展的影响，即诱导大鼠癫痫易感性增强所需的刺激诱发后放电次数。丙戊酸盐表现出强大的抗癫痫发生作用，这在诱导点燃所需的后放电次数呈剂量依赖性增加中很明显。这些作用并非由于残留的丙戊酸盐或活性代谢物仅仅掩盖了点燃性癫痫发作的表现。相比之下，卡马西平尽管表现出明显的抗惊厥作用，但没有任何抗癫痫发生作用。与丙戊酸盐一样，苯巴比妥也表现出抗癫痫发生和抗惊厥特性，但其抗癫痫发生特性明显不那么显著。丙戊酸盐和苯巴比妥的抗癫痫发生作用增强了这些药物作为临床研究候选药物的可能性，这些临床研究旨在调查高危人群中癫痫发展的药理学预防。
