Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Biol Psychiatry. 2010 Nov 15;68(10):964-70. doi: 10.1016/j.biopsych.2010.08.026.
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.
Twelve subjects were enrolled. Plasma armodafinil levels were obtained. In vivo armodafinil occupancy of the DAT in striatum was detected by [¹¹C]altropane and changes in extracellular dopamine were detected by indirect displacement of [¹¹C]raclopride in human subjects at different times after drug administration.
Armodafinil (100 mg by mouth [PO]) occupied striatal DAT (34.0 ± 9.0% at 1 hour, 40.4 ± 9.5% at 2.5 hours, n = 6) and 250 mg occupied striatal DAT (60.5 ± 7.4% at 1 hour, 65.2 ± 6.1% at 2.5 hours, n = 6). In addition, armodafinil was associated with changes in extracellular dopamine (17.8 ± 30.1% [100 mg PO] and 7.0 ± 8.6% [250 mg PO] at 2.5 hours, n = 6).
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.
阿莫达非尼主要用于治疗嗜睡症，目前正在评估其治疗其他神经精神疾病和医学病症的潜力。阿莫达非尼的神经化学基础和机制尚未明确。我们提出假设，阿莫达非尼通过调节多巴胺转运体（DAT）的活性来增强觉醒。通过正电子发射断层扫描成像，我们确定了阿莫达非尼在体内对 DAT 的占有率以及对细胞外多巴胺的影响。
共纳入 12 名受试者。检测了血浆中的阿莫达非尼水平。通过[¹¹C]altropane 检测体内阿莫达非尼对纹状体 DAT 的占有率，通过间接置换[¹¹C]raclopride 检测给药后不同时间点人体细胞外多巴胺的变化。
阿莫达非尼（口服 100mg）占据纹状体 DAT（1 小时时 34.0 ± 9.0%，2.5 小时时 40.4 ± 9.5%，n=6），250mg 时占据纹状体 DAT（1 小时时 60.5 ± 7.4%，2.5 小时时 65.2 ± 6.1%，n=6）。此外，阿莫达非尼与细胞外多巴胺的变化有关（2.5 小时时 17.8 ± 30.1%[100mg PO]和 7.0 ± 8.6%[250mg PO]，n=6）。
DAT 占有率和体内细胞外多巴胺的变化进一步表明阿莫达非尼对 DAT 的作用可能是其改善觉醒和其他病症的治疗作用的候选机制。
