Oral D-amphetamine causes prolonged displacement of [11C]raclopride as measured by PET
Oral D-amphetamine causes prolonged displacement of [11C]raclopride as measured by PET
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DOI：
10.1002/syn.10282
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发表时间：
2004-01-01
期刊：
影响因子：
2.3
通讯作者：
Busto, UE
中科院分区：
文献类型：
--
作者：
C치rdenas, L;Houle, S;Busto, UE
根据正电子发射断层扫描(PET)技术的测量，肠外注射D-苯丙胺已被用作释放多巴胺的挑战药物，多巴胺反过来又抑制[C-11]拉氯必利与多巴胺能D-2受体的结合。这项研究的主要目的是确定口服D-苯丙胺是否会以类似于静脉注射D-苯丙胺的方式抑制[C-11]拉氯普利的结合。第二个目标是评估这些影响的时间表。12名健康人体志愿者参与了这项研究。受试者分别在服药前和服药后2小时(n=5)、服药后基线和服药后2小时和6小时(n=4)、服药后基线和服药后2小时和24小时(n=3)进行扫描。口服D-苯丙胺后2小时[C-11]拉氯普利结合率显著降低(13%+/-5%)。尽管生理效应已完全恢复到基线水平，但受体利用率在6h仍下降(18%+/-6%)。[C-11]拉氯普利结合在24小时后恢复到基线水平。[C-11]拉氯普利排泄量百分比与血浆D-苯丙胺浓度无关。总之，口服D-苯丙胺可引起可靠而持久的[C-11]拉氯普利移位，其幅度与静脉给药后相似。观察到的长时间移位的可能机制可能包括突触内多巴胺的持续和/或受体内化。Synapse 51：27-31,2004。(C)2003年Wiley-Liss，Inc.
Parenterally administered D-amphetamine has been used as a challenge drug to release dopamine, which in turns inhibits [C-11]raclopride binding to dopaminergic D-2 receptors as measured using positron emission tomography (PET) techniques. The primary objective of this study was to determine whether orally administered D-amphetamine would inhibit [C-11]raclopride binding in a manner similar to that produced by intravenously administered D-amphetamine. The secondary objective was to assess the timeline of these effects. Twelve healthy human volunteers participated in this study. Subjects were scanned at baseline and 2 h after D-amphetamine administration (n = 5); at baseline, 2 and 6 h postdrug (n = 4); or at baseline, 2 and 24 h postdrug (n = 3). Orally administered D-amphetamine caused a significant decrease in [C-11]raclopride binding at 2 h (13% +/- 5%). Receptor availability was still decreased at 6 h (18% +/- 6%), even though physiological effects had completely returned to baseline. [C-11]Raclopride binding returned to baseline at 24 h. The percentage of [C-11]raclopride displacement was not correlated with plasma D-amphetamine concentrations. In conclusion, orally administered D-amphetamine caused a reliable and prolonged [C-11]raclopride displacement, the magnitude of which is similar to that observed after intravenous administration. Possible mechanisms for the observed prolonged displacement may include persistence of intrasynaptic dopamine and/or receptor internalization. Synapse 51:27-31, 2004. (C) 2003 Wiley-Liss, Inc.