CENTRAL AND PERIPHERAL ACTIONS OF AMPHETAMINE IN ADHD

安非他明在 ADHD 中的中枢和末梢作用

• 批准号: 3430050
• 负责人: Robert Keith McBurnett
• 金额: $ 7.14万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3430050
• 关键词: aggression; association learning; attention deficit disorder; behavior test; central nervous system; central nervous system stimulants; child (0-11); child behavior; dextroamphetamine; dosage; drug administration rate /duration; drug adverse effect; human subject; human therapy evaluation; learning stimulant; male; memory; mental disorder chemotherapy; pediatric pharmacology; performance; peripheral nervous system; psychomotor function; social behavior

The proposed study has the broad goal of elucidating the mechanisms underlying the therapeutic action of amphetamine in Attention Deficit- Hyperactivity Disorder (ADHD). The form of amphetamine that is currently used to treat ADHD (d-amphetamine or Dexedrine) has both central and peripheral action. A form of amphetamine that has only peripheral direct action (4-OH amphetamine) has been shown to affect learning in animals. We plan to investigate whether experimental laboratory measures or clinical symptoms are affected by 4-OH amphetamine through a peripheral mechanism that subsequently modulates CNS activity. Several hypotheses that have theoretical and clinical significance will be tested. First, a subset of ADHD symptoms is predicted to respond to 4-OH amphetamine. Second, this peripherally acting stimulant is hypothesized to show fewer or milder side effects that stimulants with central action. Third, dose-response curves for the different stimulants are expected to show the phenomenon of "cognitive toxicity" (deterioration of improvement in effortful learning) . The specific aims of the study are (a) to compare the safety and side effects of 4-OH amphetamine to those of the form of amphetamine in clinical use (d-amphetamine), and (b) to compare dose-response curves for d-, and 4-OHG amphetamine on paired-associate learning, effortful memory scanning, disruptive social behavior, response to behavioral contingencies, motor activity, and side effects in children with ADHD who have been diagnosed as having ADHD. The first aim will be achieved by a medically supervised open trial of single administrations of three doses (.15, .3, and .5 mg/kg) of 4-OH and d-amphetamine. The second aim will be achieved using a within-subjects crossover experimental design in which each child will be assessed after receiving each of four doses (0, .15, .3, and .5 mg/kg) of d, dl, and 4-OH amphetamine for one-week durations. Data from this 3 x 4 (drug x dose) factorial design will be evaluated using analysis of variance and trend analysis.

这项研究的目标是阐明 安非他明对注意力缺陷的治疗作用 多动症（ADHD）。 安非他明的形式，目前是 用于治疗ADHD（d-安非他明或右旋苯丙胺）的药物既有中枢神经系统， 外围动作 安非他明的一种形式，只有外周直接 作用（4-OH安非他明）已被证明会影响动物的学习能力。 我们计划调查实验室测量或 临床症状受4-OH安非他明通过外周 随后调节CNS活性的机制。 几个假说 具有理论和临床意义的研究。 一是 ADHD症状的一个子集被预测对4-OH安非他明有反应。 其次，这种外周作用的兴奋剂被假设为显示较少 或者说副作用比中枢作用的兴奋剂更轻微。 第三、 不同兴奋剂的剂量反应曲线预计将显示 “认知毒性”现象（改善的恶化）， 努力学习）。 本研究的具体目的是（a）比较安全性和 4-OH安非他明的副作用，以那些形式的安非他明， 临床应用（d-安非他明），和（B）比较以下的剂量-反应曲线： d-和4-OHG苯丙胺对配对联想学习、努力记忆的影响 扫描，破坏性社会行为，对行为的反应， 注意缺陷多动障碍儿童的意外事件、运动活动和副作用， 被诊断为多动症 第一个目标将通过一个 医学监督下的三剂单次给药开放试验 (.15、0.3和0.5 mg/kg）的4-OH和d-苯丙胺。 第二个目标将 使用受试者内交叉实验设计， 每个儿童在接受四个剂量中的每一个之后将被评估（0， 0.15、0.3和0.5 mg/kg）d、dl和4-OH安非他明，持续一周 持续时间。 来自该3 x 4（药物x剂量）析因设计的数据将 使用方差分析和趋势分析进行评价。