ADHD Treatment & Amphetamine Neurotoxicity

多动症治疗

• 批准号: 6918924
• 负责人: GEORGE A RICAURTE
• 金额: $ 37.28万
• 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/6918924
• 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）：注意力缺陷多动障碍 (ADHD) 是一种常见的致残性神经精神疾病，影响 3-7% 的儿童和 1-5% 的成人。兴奋剂药物是治疗多动症的主要方法。在用于治疗多动症的各种兴奋剂药物中，安非他明是最常给儿童和成人开处方的药物之一。大量数据表明，安非他明有可能破坏动物的大脑多巴胺 (DA) 轴突和轴突末端。人类接受安非他明治疗 ADHD 可能会产生类似的安非他明诱导的 DA 神经毒性的可能性尚未得到研究，主要是因为在动物中产生 DA 神经毒性作用的剂量（按 ing/kg 计算）高于用于治疗的剂量。多动症的治疗。然而，我们实验室最近的初步研究结果表明，狒狒口服安非他明剂量方案与通常用于治疗多动症的方案相似，可以维持纹状体中 DA 神经毒性的变化。试验数据还表明，狒狒中与大脑 DA 神经毒性相关的安非他明血浆水平与接受安非他明治疗 ADHD 的人类报告的水平相当。拟议研究的目的是：1）证实我们对大量成年狒狒的初步观察，并看看它们是否可以扩展到青春期动物； 2) 确定狒狒身上的发现是否可以推广到已知以与人类类似的方式代谢安非他明的另一种非人类灵长类动物（松鼠猴、成年和青少年）； 3) 测量非人类灵长类动物中苯丙胺给药方案产生的苯丙胺血浆浓度，以便将两种非人类灵长类动物中与 DA 神经毒性相关的苯丙胺水平和药代动力学特征与先前记录的人类中的水平和药代动力学特征进行比较。总之，拟议研究的结果将有助于确定是否有必要对接受安非他明治疗 ADHD 的人类可能引起的 DA 神经毒性感到担忧，以及是否需要对人类 ADHD 人群中苯丙胺可能引起的 DA 神经毒性进行对照研究。