Holmes Gregory L, Zhao Qian
Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA.
Pediatr Neurol. 2008 Mar;38(3):151-62. doi: 10.1016/j.pediatrneurol.2007.09.008.
Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy is directed primarily toward reducing excitability through blockage of voltage-gated Na(+) or Ca(2+) channels, or increasing inhibition through enhancement of gamma-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals (usually rodents). Maximal electrical shock, pentylenetetrazol, and kindling are typically used as nonmechanistic screens for antiseizure properties, and the rotorod test assesses acute toxicity. Whereas antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it merits emphasis that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than in adults. Despite these age-related unique features, drugs used in children are generally the same as those in adults. As awareness of the unique features of seizures during development increases, more drug screening in the immature animal will likely occur.
癫痫是一种由大脑中正常兴奋性和抑制性力量失衡引起的慢性疾病。抗癫痫药物治疗主要旨在通过阻断电压门控钠（Na⁺）通道或钙（Ca²⁺）通道来降低兴奋性，或通过增强γ-氨基丁酸电流来增强抑制作用。在进行临床研究之前，假定的抗癫痫药物会在动物（通常是啮齿动物）中进行筛选。最大电休克、戊四氮和点燃通常用作抗癫痫特性筛选的非机制性模型，旋转棒试验则评估急性毒性。虽然抗癫痫药物筛选已成功将药物推向市场并增进了我们对癫痫发作病理生理学的理解，但值得强调的是，绝大多数药物筛选是在成年雄性啮齿动物中进行的，且涉及癫痫发作模型而非癫痫模型。对急性癫痫发作有效的药物在慢性癫痫模型中可能无效。癫痫患儿的发作类型、临床和脑电图表型、综合征及病因通常与成人有很大差异。尽管存在这些与年龄相关的独特特征，但儿童使用的药物通常与成人相同。随着人们对发育过程中癫痫发作独特特征的认识不断提高，在未成熟动物中进行的药物筛选可能会增多。
