DRUG RECEPTORS IN VIVO

在可卡因成像领域取得了相当大的进展 活体动物的受体。 我们的第一个努力是利用一个已知的 抗抑郁药诺米芬辛 体内结合的详细研究 这种化合物的特征表明，它定位于多巴胺， 转运蛋白非常有效，但具有低特异性至非特异性 结合率正因为如此，我们着手开发更高效的 结合配体。 我们实验室以前的研究表明可卡因类似物， WIN-35，065 -2和WIN-35，428是多巴胺的较好配体 转运蛋白的特异性与非特异性结合率较高， 在体内获得。 最近，我们使用WIN-35，428在一个更 广泛的研究最终表明这种化合物 可卡因受体/多巴胺转运蛋白的作用。 我们正在 利用该化合物以其正电子发射形式携带 体内多巴胺转运蛋白的PET扫描研究。 体内标记技术的一个重要用途是检查 各种药物在体内占据受体的能力。 因为 我们使用WIN-35，428的体内标记模型的可用性，我们能够 为了检测马吲哚对可卡因受体的相对占据率， GBR-12,909和可卡因。 我们清楚地表明可卡因进入大脑 并且比马吲哚或马吲哚更快地占据可卡因受体， 12909英镑 众所周知，滥用药物的可能性更大， 进入大脑并迅速占据受体。 因此，该模型将 用于定量评估药物进入大脑的速度， 占据受体;这将有助于定量 这一因素的滥用责任评估的知识。

Considerable progress has been made in the area of imaging cocaine receptors in living animals. Our first efforts involved utilizing a known antidepressant drug, nomifensine. A detailed study of the in vivo binding characteristics of this compound revealed that it localized to dopamine transporters quite effectively but with a low specific to non-specific binding ratio. Because of this, we set out to develop more efficient binding ligands. Studies from our laboratory previously showed that cocaine analogs, WIN-35,065-2 and WIN-35,428 were better ligands for the dopamine transporter in that higher specific to non-specific binding ratios were obtained in vivo. More recently, we utilized WIN-35,428 in a more extensive study which conclusively showed that this compound localized to cocaine receptors/dopamine transporters in rat striatum. We are in the process of utilizing this compound in its positron emitting form to carry out PET scanning studies of dopamine transporters in vivo. One important use of in vivo labelling techniques is to examine the rate of occupancy of receptors in vivo by various drugs. Because of the availability of our in vivo labeling model using WIN-35,428, we were able to examine the relative rate of occupancy of cocaine receptor by mazindol, GBR-12,909 and cocaine. We clearly showed that cocaine enters the brain and occupies cocaine receptors much more rapidly than mazindol or GBR-12,909. It is known that abuse liability is greater for drugs that enter the brain and occupy receptors rapidly. Thus, this model will be useful in quantitatively assessing how rapidly drugs enter the brain and occupy receptors; this will be helpful in contributing quantitative knowledge of this factor for abuse liability assessment.