Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Psychopharmacology (Berl). 2010 Jun;210(3):331-6. doi: 10.1007/s00213-010-1824-9. Epub 2010 Mar 23.
Central norepinephrine transporter (NET) is one of the main targets of antidepressants. Although the measurement of NET occupancy has been attempted in humans, the outcomes have been inconclusive.
In this study, the occupancy of NET by different doses of an antidepressant, nortriptyline, was measured using positron emission tomography (PET) with (S,S)-[(18)F]FMeNER-D(2).
PET scans using (S,S)-[(18)F]FMeNER-D(2) were performed on six healthy men before and after oral administration of a single oral dose of nortriptyline (10-75 mg). After a bolus i.v. injection of (S,S)-[(18)F]FMeNER-D(2), dynamic scanning was performed for 0-90 min, followed by scanning for 120-180 min. The ratio of the thalamus-to-caudate areas under the curve (120-180 min) minus 1 was used as the binding potential (BP(ND)) for NET. NET occupancy was calculated as the percentage reduction of BP(ND). Venous blood samples were taken to measure the concentrations of nortriptyline just before injection of the tracer and at 180 min after the injection.
Mean NET occupancies by nortriptyline were 16.4% at 10 mg, 33.2% at 25 mg, and 41.1% at 75 mg. The mean plasma concentration of nortriptyline was less than the lower limit of detection at 10 mg, 23.7 ng/mL at 25 mg, and 50.5 ng/mL at 75 mg. Estimated ED(50) was 76.8 mg of administration dose and 59.8 ng/mL of plasma concentration.
NET occupancy by nortriptyline corresponding to the administration dose of 10-75 mg or plasma concentration was observed from 16% to 41%.
中枢去甲肾上腺素转运体（NET）是抗抑郁药的主要靶点之一。尽管已经尝试在人体中测量 NET 占有率，但结果尚无定论。
在这项研究中，使用正电子发射断层扫描（PET）和（S，S）-[（18）F] FMeNER-D（2）测量不同剂量的抗抑郁药，去甲丙咪嗪对 NET 的占有率。
在口服单剂量去甲丙咪嗪（10-75mg）之前和之后，对六名健康男性进行了（S，S）-[（18）F] FMeNER-D（2）的 PET 扫描。静脉内推注（S，S）-[（18）F] FMeNER-D（2）后，进行 0-90min 的动态扫描，然后进行 120-180min 的扫描。丘脑-尾状核区（120-180min）下曲线的比率减去 1 被用作 NET 的结合潜力（BP（ND））。NET 占有率计算为 BP（ND）减少的百分比。在注射示踪剂之前和注射后 180 分钟采集静脉血样以测量去甲丙咪嗪的浓度。
去甲丙咪嗪的平均 NET 占有率分别为 10mg 时为 16.4%，25mg 时为 33.2%，75mg 时为 41.1%。10mg 时去甲丙咪嗪的平均血浆浓度低于检测下限，25mg 时为 23.7ng/mL，75mg 时为 50.5ng/mL。估计 ED（50）为 76.8mg 给药剂量和 59.8ng/mL 的血浆浓度。
观察到去甲丙咪嗪的 NET 占有率从 16%到 41%，对应于 10-75mg 的给药剂量或血浆浓度。
