Jones A K, Luthra S K, Maziere B, Pike V W, Loc'h C, Crouzel C, Syrota A, Jones T
Service Hospitalier Frédéric Joliot, Dept. de Biologie, Hôspital d'Orsay, France.
J Neurosci Methods. 1988 Mar;23(2):121-9. doi: 10.1016/0165-0270(88)90184-7.
The results are described of the cerebral uptake and heterogeneous retention of [11C]diprenorphine after intravenous injection in 4 normal volunteers. This potent opioid antagonist (Kd = 0.2 nM) was chosen because of its safety, lack of side-effects at trace doses in human pilot studies, rapid cerebral uptake and high percentage (80-90%) specific binding in animal in vivo studies. High uptake of [11C]diprenorphine was demonstrated in regions such as the thalamus, caudate nucleus, temporal, frontal and parietal cortices, which are known from postmortem studies to have high concentrations of opioid receptors. A stable level of activity or a very slow decline in activity was observed between 20 and 50 min after injection in areas such as the caudate nucleus and thalamus. Conversely, rapid washout of activity was observed in the occipital cortex, which is known to have low opioid receptor concentrations. Some 80-90% of maximum binding was naloxone reversible. These results with a ligand that is safe and without side-effects, suggest that this technique is suitable for studies of opioid physiology in man.
本文描述了4名正常志愿者静脉注射[11C]二丙诺啡后脑摄取及异质性滞留的结果。选择这种强效阿片类拮抗剂（Kd = 0.2 nM）是因为其安全性高、在人体预试验中微量给药时无副作用、脑摄取迅速以及在动物体内研究中特异性结合率高（80 - 90%）。[11C]二丙诺啡在丘脑、尾状核、颞叶、额叶和顶叶皮质等区域摄取较高，尸检研究表明这些区域阿片受体浓度较高。在注射后20至50分钟之间，尾状核和丘脑等区域的放射性活性水平稳定或下降非常缓慢。相反，枕叶皮质放射性活性迅速清除，已知该区域阿片受体浓度较低。最大结合量的约80 - 90%可被纳洛酮逆转。这些使用安全且无副作用配体的结果表明，该技术适用于人体阿片类生理学研究。
