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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目标：所有治疗注意力缺陷多动障碍（ADHD）的药物都会通过多巴胺（DAT）和/或去甲肾上腺素（NET）转运蛋白减弱多巴胺（DA）和去甲肾上腺素（NE）的转运。微量胺与ADHD有关，因为在一些报告中，ADHD男性儿童尿液中的微量胺苯乙胺（PEA）减少，并通过抗ADHD药物恢复正常。由于潜在的机制未知，我们假设ADHD药物通过DAT或NET阻断PEA转运使ADHD儿童的PEA水平正常化。方法：我们确定ADHD药物（哌甲酯，（+）-安非他明，托莫西汀，莫达非尼）是否影响DAT和NET的（3 H）PEA转运。 研究结果：哌醋甲酯阻断DAT转运（3 H）PEA的效力是阻断（3 H）DA转运的效力的近2倍，并且哌醋甲酯还有效地阻断NET转运（3 H）PEA。（+）-安非他明阻断（3 H）PEA转运的效力比（3 H）DA转运的效力低3倍。托莫西汀是DAT转运的（3 H）DA或（3 H）PEA的弱抑制剂，是NET的强效抑制剂莫达非尼（在体内占据DAT和NET）是DAT转运的相对弱抑制剂，但阻断（3 H）PEA的效力略高于（3 H）DA转运。其他治疗药物，马吲哚，诺米芬辛，苯扎托品安非他酮，阻断（3 H）PEA比（3 H）DA转运的效力高2-4倍。结论：可以想象，抗多动症药物阻断PEA转运可以解释ADHD男性儿童尿PEA水平的正常化。这些结果表明，在针对DAT和NET的ADHD药物的治疗反应中存在微量胺、转运蛋白和微量胺受体1。