丙戊酸：第二代。
Valproic Acid: second generation.
作者信息
Bialer Meir, Yagen Boris
机构信息
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
出版信息
Neurotherapeutics. 2007 Jan;4(1):130-7. doi: 10.1016/j.nurt.2006.11.007.
The manuscript focuses on structure-activity relationship studies of CNS-active compounds derived from valproic acid (VPA) that have the potential to become second-generation VPA drugs. Valproic acid is one of the four most widely prescribed antiepileptic drugs (AEDs) and is effective (and regularly approved) in migraine prophylaxis and in the treatment of bipolar disorders. Valproic acid is also currently undergoing clinical trials in cancer patients. Valproic acid is the least potent of the established AEDs and its use is limited by two rare but potentially life-threatening side effects, teratogenicity and hepatotoxicity. Because AEDs treat the symptoms (seizure) and not the cause of epilepsy, epileptic patients need to take AEDs for a long period of time. Consequently, there is a substantial need to develop better and safer AEDs. To become a successful second-generation VPA, the new drug should possess the following characteristics: broad-spectrum antiepileptic activity, better potency than VPA, lack of teratogenicity and hepatotoxicity, and a favorable pharmacokinetic profile compared with VPA including a low potential for drug interactions.
该手稿聚焦于源自丙戊酸（VPA）的具有中枢神经系统活性的化合物的构效关系研究，这些化合物有可能成为第二代VPA药物。丙戊酸是四种最广泛处方的抗癫痫药物（AEDs）之一，在偏头痛预防和双相情感障碍治疗中有效（且经常被批准使用）。丙戊酸目前也正在癌症患者中进行临床试验。丙戊酸是已确定的AEDs中效力最低的，其使用受到两种罕见但可能危及生命的副作用——致畸性和肝毒性的限制。由于AEDs治疗的是症状（癫痫发作）而非癫痫的病因，癫痫患者需要长期服用AEDs。因此，迫切需要开发更好、更安全的AEDs。要成为成功的第二代VPA，新药应具备以下特性：广谱抗癫痫活性、比VPA更高的效力、无致畸性和肝毒性，以及与VPA相比有利的药代动力学特征，包括药物相互作用的可能性低。
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