Somatostatin Mimetics as Novel Anti-Epileptic Drugs

生长抑素模拟物作为新型抗癫痫药物

• 批准号: 6645137
• 负责人: GIDEON SHAPIRO
• 金额: $ 10.14万
• 依托单位: RFE PHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2004-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6645137
• 关键词: anticonvulsants; biomimetics; biotherapeutic agent; blood brain barrier; chemical synthesis; drug design /synthesis /production; drug screening /evaluation; high performance liquid chromatography; hydropathy; imidazolidone; laboratory rat; limbic system; neuropeptide receptor; partial seizure; peptide hormone analog; pharmacokinetics; receptor binding; somatostatin; temporal lobe /cortex disorder

DESCRIPTION (provided by applicant): The epilepsies are a family of neurological disorders characterized by seizures which are transient, recurrent perturbations of normal brain function. As a chronic condition, epilepsy affects about 1 percent of the population in the United States. While anti-epileptic drug (AED) treatment is the standard therapy for epilepsy, one third of all patients remain unresponsive to currently available medications. A growing body of research indicates that controlling seizure activity is an important physiological function for somatostatin in the CNS. Therefore, centrally active somatostatin analogs have potential to be novel, effective AEDs with a well defined molecular mechanism of action. A new structural class of potent non-peptide somatostatin mimetics with demonstrated CNS activity provides the starting point of the plan. This class of compounds will be optimized for in vitro potency and lipophilicity. Potential CNS drugs selected based on these in vitro parameters will be screened in vivo for efficacy in the acute seizure, rat kindling model of epilepsy. The rat chronic limbic epilepsy model will be used (largely in Phase II) to screen for compounds that are also active against spontaneous seizures and therefore have the greatest potential for demonstrating clinical efficacy in man.

描述（由申请人提供）：癫痫是一类神经系统疾病，其特征是癫痫发作是对正常脑功能的短暂、反复的干扰。作为一种慢性疾病，癫痫症影响着美国约 1% 的人口。虽然抗癫痫药物 (AED) 治疗是癫痫的标准治疗方法，但三分之一的患者对目前可用的药物仍然没有反应。越来越多的研究表明，控制癫痫活动是中枢神经系统中生长抑素的重要生理功能。因此，具有中枢活性的生长抑素类似物有潜力成为新型、有效的 AED，具有明确的分子作用机制。具有中枢神经系统活性的一类新结构的强效非肽生长抑素模拟物为该计划提供了起点。此类化合物将针对体外效力和亲脂性进行优化。根据这些体外参数选择的潜在中枢神经系统药物将在体内筛选其在急性癫痫发作、大鼠癫痫点燃模型中的疗效。大鼠慢性边缘癫痫模型将用于（主要在第二阶段）筛选对自发性癫痫发作也具有活性的化合物，因此最有可能在人类中证明临床疗效。