PHENETHYLAMINE (PEA) AND ATTENTION DEFICIT HYPERACTIVITY DISORDER

苯乙胺 (PEA) 和注意力缺陷多动障碍

• 批准号: 8172880
• 负责人: Bertha K Madras
• 金额: $ 1.81万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172880
• 关键词: Accounting; Affect; Amines; Amphetamines; Attention deficit hyperactivity disorder; Attenuated; Benztropine; Bupropion; Child; Computer Retrieval of Information on Scientific Projects Database; Dopamine; Funding; Grant; Hyperactive behavior; Institution; Mazindol; Methylphenidate; Modafinil; Nomifensine; Norepinephrine; Pharmaceutical Preparations; Phenethylamines; Reporting; Research; Research Personnel; Resources; Source; Therapeutic; Time; United States National Institutes of Health; Urine; atomoxetine; in vivo; inhibitor/antagonist; male; response; urinary

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. AIMS: All medications that treat attention deficit hyperactivity disorder (ADHD) attenuate the transport of dopamine (DA) and norepinephrine (NE), via the dopamine (DAT) and/or norepinephrine (NET) transporters. Trace amines have been implicated in ADHD, as the trace amine phenethylamine (PEA) is reduced in urines of ADHD male children and normalized by anti-ADHD medications, in some reports. With the underlying mechanisms unknown, we postulated that ADHD medications normalize PEA levels in ADHD children by blockade of PEA transport by the DAT or NET. METHODS: We determine whether ADHD medications (methylphenidate, (+)-amphetamine, atomoxetine, modafinil) affected (3H)PEA transport by the DAT and the NET. RESULTS: Methylphenidate was nearly 2-fold more potent at blocking (3H)PEA than (3H)DA transport by the DAT and also potently blocked (3H)PEA transport by the NET. (+)-Amphetamine was 3-fold less potent at blocking (3H)PEA than (3H)DA transport. Atomoxetine was a weak inhibitor of (3H)DA or (3H)PEA transport by the DAT and a potent inhibitor at the NET Modafinil, which occupies the DAT and the NET in vivo, was a relatively weak inhibitor of DAT transport, but was slightly more potent at blocking (3H)PEA than (3H)DA transport. Other therapeutic drugs, mazindol, nomifensine, benztropine bupropion, were 2-4 times more potent at blocking (3H)PEA than (3H)DA transport. CONCLUSIONS: Conceivably, blockade of PEA transport by anti-hyperactivity medications accounts for normalization of urinary PEA levels in ADHD male children. These results implicate trace amines, transporters and the trace amine receptor1 in the therapeutic response of ADHD medications which target DAT and NET.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：所有治疗注意缺陷多动障碍(ADHD)的药物都能减弱多巴胺(DA)和去甲肾上腺素(NE)通过多巴胺(DAT)和/或去甲肾上腺素(NET)转运蛋白的转运。在一些报道中，痕量胺与ADHD有关，因为ADHD男性儿童尿中的痕量苯乙胺(PEA)减少，并被抗ADHD药物正常化。由于潜在的机制尚不清楚，我们推测ADHD药物通过阻断DAT或Net的PEA转运而使ADHD儿童的PEA水平正常化。方法：用DAT和Net检测ADHD药物(哌醋甲酯、(+)-苯丙胺、托莫西汀、莫达非尼)对(3 H)PEA转运的影响。结果：哌甲酸甲酯阻断(3 H)PEA的能力是DAT(3 H)DA转运的近2倍，也能有效地阻断(3 H)PEA的网络转运。(+)-苯丙胺阻断(~3H)PEA的能力是(~3H)DA转运的3倍。托莫西汀是DAT转运(~3H)DA或(~3H)PEA的弱抑制剂，在体内占据DAT和Net的莫达非尼是一种强有力的抑制剂，对DAT转运的抑制作用相对较弱，但对(~H)PEA的阻断作用略强于(~3H)DA转运。其他治疗药物，马吲哚、诺米芬辛、苯妥拉平安非他酮，对(~H)PEA的阻断作用是(~H)DA转运的2-4倍。结论：可以想象，抗多动药物阻断PEA转运是ADHD男性儿童尿中PEA水平正常化的原因。这些结果表明，在针对DAT和NET的ADHD药物的治疗反应中，痕量胺、转运体和痕量胺受体1参与其中。