Novel Serotonin Reuptake Inhibitors for Autism Treatment

用于治疗自闭症的新型血清素再摄取抑制剂

• 批准号: 6754670
• 负责人: Kevin G. Pinney
• 金额: $ 17.23万
• 依托单位: BAYLOR UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-23 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6754670
• 关键词: antipsychotic agents; autism; chemical information system; chemical structure function; combinatorial chemistry; drug design /synthesis /production; drug screening /evaluation; human tissue; inhibitor /antagonist; laboratory rat; mass spectrometry; mental disorder chemotherapy; neurotransmitter transport; nuclear magnetic resonance spectroscopy; psychopharmacology; receptor binding; serotonin inhibitor; serotonin receptor; serotonin transporter

DESCRIPTION (provided by applicant): Clinical evidence has shown that selective serotonin reuptake inhibitors (SSRIs) and "atypical" antipsychotics are drugs commonly used and proven effective for the treatment of some of the most important and incapacitating symptoms associated with autism spectrum disorders. SSRIs have been identified by researchers and patients' families as some of the most clinically useful agents, especially in targeting repetitive preoccupations, perseverative behaviors and anxiety-related symptoms. Atypical antipsychotics have also proven effective for improving other types of symptoms such as hyperactivity, and in reducing the frequency and intensity of temper outbursts and aggression in patients with autism. Nevertheless, these currently available drugs still face an undesired side effect profile that limits their use, especially in treating young children. The proposed research program focuses on the synthesis and biological evaluation of novel bi-functional molecules that, by incorporating into one molecular entity the biological effects of both SSRIs and atypical antipsychotics, can provide synergism in terms of their potential efficacy over a wider variety of the core symptoms in patients with autism. In order to develop the proposed bi-functional molecules, we have designed and plan to prepare a series of new drug candidates, which judiciously combine portions of SSRIs with known 5-HT2A receptor antagonists. This is a pilot research study, which represents an innovative approach to the pharmacological treatment of autism. It can be extremely beneficial since it has the strong potential to overcome the drawbacks of two separate pharmacological treatments, which include high costs and undesired side effects. Biological evaluation of the proposed molecules will provide valuable information about the structural features necessary to achieve strong and highly selective binding to both target sites, and give preliminary evidence in regard to whether the new molecules represent valuable "lead" compounds for further in vitro and in vivo investigations. Finally, we believe that this study supports the mission of NIH in its ongoing search for effective treatments for autistic disorder as well as for depressive illnesses, and that the results obtained by this research, will further advance our understanding of autism and lead to improved treatment methods.

描述（由申请人提供）：临床证据表明，选择性血清素再摄取抑制剂（SSRI）和“非典型”抗精神病药是常用药物，并被证明可有效治疗与自闭症谱系障碍相关的一些最重要和失能的症状。 SSRIs 已被研究人员和患者家属认为是临床上最有用的药物之一，特别是在针对重复性专注、持续行为和焦虑相关症状方面。非典型抗精神病药也被证明可以有效改善其他类型的症状，例如多动症，以及减少自闭症患者发脾气和攻击性的频率和强度。然而，这些目前可用的药物仍然面临不良副作用，限制了它们的使用，特别是在治疗幼儿时。拟议的研究计划侧重于新型双功能分子的合成和生物学评估，通过将 SSRIs 和非典型抗精神病药的生物效应纳入一个分子实体，可以在更广泛的药物中提供其潜在功效方面的协同作用。自闭症患者的核心症状。为了开发所提出的双功能分子，我们设计并计划制备一系列新候选药物，这些候选药物明智地将部分 SSRI 与已知的 5-HT2A 受体拮抗剂结合起来。这是一项试点研究，代表了自闭症药物治疗的创新方法。它非常有益，因为它具有克服两种单独药物治疗的缺点的强大潜力，其中包括高成本和不良副作用。对所提出的分子的生物学评估将提供有关实现与两个靶位点的强和高选择性结合所需的结构特征的有价值的信息，并提供关于新分子是否代表有价值的“先导”化合物以用于进一步的体外和体内实验的初步证据。体内调查。最后，我们相信这项研究支持 NIH 的使命，即不断寻找自闭症和抑郁症的有效治疗方法，并且这项研究获得的结果将进一步增进我们对自闭症的理解并改善治疗方法方法。