ADHD Treatment & Amphetamine Neurotoxicity

多动症治疗

• 批准号: 7093553
• 负责人: GEORGE A RICAURTE
• 金额: $ 37.6万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093553
• 关键词: Saimiri; amphetamines; attention deficit disorder; autoradiography; baboons; dopamine; drug adverse effect; juvenile animal; mental disorder chemotherapy; neurons; neurotoxicology; pharmacokinetics

DESCRIPTION (provided by applicant): Attention deficit hyperactivity disorder (ADHD) is a common and disabling neutopsychiatric disorder that afflicts 3-7% of children and 1-5% of adults. Stimulant drugs are the mainstay of treatment for ADHD. Of the various stimulant drugs used to treat ADHD, amphetamine is among the most often prescribed, both to children and adults. A significant body of data indicates that amphetamine has the potential to destroy brain dopamine (DA) axons and axon terminals in animals. The possibility that humans receiving amphetamine for the treatment of ADHD might incur similar amphetamine-induced DA ncurotoxicity has not been investigated, largely because the doses that produce DA neurotoxic effects in animals are higher, on a ing/kg basis, than the doses used in the treatment of ADHD. However, recent preliminary findings in our laboratory indicate that baboons treated with an oral dosing regimen of amphetamine similar to that used commonly to treat ADHD sustain DA neurotoxic changes in the striatum. Pilot data also indicate that plasma levels of .amphetamine associated with brain DA ncurotoxicity in baboons are on the order of those reported in humans treated with amphetamine for ADHD. The aims of the proposed studies are: 1) To confirm our preliminary observations in a larger number of adult baboons, and to see if they can be extended to adolescent animals; 2) To determine if findings in baboons can be extended to another non-human primate species (squirrel monkeys, adult and adolescent) known to metabolize amphetamine in a manner similar to humans ; and 3) To measure plasma concentrations of amphetamine engendered by dosing regimens of amphetamine in non-human primates, in order to compare the levels and pharmacokinctic profiles of amphetamine associated with DA ncurotoxicity in 2 non-human primate species with those previously documented in humans. Together, results of the proposed studies will help determine whether concern over possible amphetamineinduced DA neurotoxicity in humans receiving amphetamine for the treatment of ADHD is warranted, and if controlled studies of possible amphetamine-induced DA neurotoxicity in human ADHD cohorts are indicated.

描述（由申请人提供）：注意力缺陷多动症（ADHD）是一种常见且残疾的中性精神疾病，折磨3-7％的儿童和1-5％的成年人。刺激性药物是多动症治疗的主要手段。在用于治疗多动症的各种刺激性药物中，苯丙胺是儿童和成人最常见的。大量数据表明，苯丙胺有可能破坏动物中脑多巴胺（DA）轴突和轴突末端。接受ADHD治疗的人类的可能性可能会引起类似的苯丙胺引起的DA NCUROTOXICIS，这很大程度上很大程度上是因为在动物中产生DA神经毒性作用的剂量比在ADHD治疗ADHD治疗的剂量的基础上更高。但是，我们实验室中最近的初步发现表明，用苯丙胺的口服给药方案治疗的狒狒类似于通常用于治疗纹状体中ADHD维持DA神经毒性变化的狒狒。试验数据还表明，狒狒中与脑毒性相关的等离子体水平是狒狒中的脑毒性相关的水平，该水平是在用苯丙胺治疗的ADHD治疗的人类中报告的。拟议的研究的目的是：1）确认我们在大量的成年狒狒中的初步观察，并查看它们是否可以扩展到青少年动物； 2）确定狒狒的发现是否可以扩展到另一种非人类灵长类动物（松鼠猴，成人和青少年），以类似于人类的方式代谢苯丙胺； 3）为了测量非人类灵长类动物中苯丙胺的给药方案产生的苯丙胺的血浆浓度，以比较2个非人类灵长类动物中与先前在人类中记录的非人类灵长类动物中的DA ncurotoxicity与DA Ncurotoxicity相关的苯丙胺的水平和药物形成型。总之，拟议的研究的结果将有助于确定是否有必要对接受ADHD治疗的人类中可能的苯胺诱导的DA神经毒性进行关注，并且是否有保证对苯丙胺诱导的DA神经毒性在人ADHD中的DA神经毒性的研究。