期刊
BIOLOGICAL PSYCHIATRY
卷 68, 期 10, 页码 964-970出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.08.026
关键词
ADHD; neurochemical imaging; PET imaging pharmacokinetics stimulants; substance abuse
资金
- Cephalon Pharmaceuticals
- Shire Laboratories Inc
- Eli Lilly Company
- GlaxoSmithKline
- Janssen Pharmaceutical
- McNeil Pharmaceutical
- Novartis Pharmaceuticals
- Cephalon
- Pfizer
- National Institute of Mental Health
- Wyeth
- Jazz Pharmaceuticals
- Bristol Myers Squibb
- Brand Ideas
- Reed Elsevier
- Medtronic
- Cyberonics
- Eli Lilly
- McNeil
- Northstar
Background Armodafinil prescribed principally to treat narcolepsy is undergoing assessment of therapeutic potential for other neuropsychiatric disorders and medical conditions The neurochemical substrates and mechanisms of armodafinil are unresolved We investigated the hypothesis that armodafinil enhances wakefulness by modulating the activities of the dopamine transporter (DAT) With positron emission tomography imaging we determined DAT occupancy and changes in extracellular dopamine by armodafinil in vivo Methods Twelve subjects were enrolled Plasma armodafinil levels were obtained In vivo armodafinil occupancy of the DAT in striatum was detected by [C-11]altropane and changes in extracellular dopamine were detected by indirect displacement of [C-11]raclopride in human subjects at different times after drug administration Results Armodafinil (100 mg by mouth [PO]) occupied striatal DAT (34 0 +/- 90% at 1 hour 404 +/- 95% at 25 hours n = 6) and 250 mg occupied striatal DAT (60 5 +/- 74% at 1 hour, 652 +/- 61% at 25 hours n = 6) In addition armodafinil was associated with changes in extracellular dopamine (17 8 +/- 30 1% [100 mg PO] and 70 +/- 86% [250 mg PO] at 2 5 hours n = 6) Conclusions Occupancy of the DAT and changes in extracellular dopamine in vivo further implicates the actions of armodafinil on DAT as a potential candidate for its therapeutic improvement of wakefulness and other conditions
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据