DOPAMINE TRANSPORTER--STRUCTURE/FUNCTION STUDIES OF TRANSPORTER AND LIGANDS

多巴胺转运蛋白（DAT）已被确定为主要的大脑 受体位点与奖赏和欣快特性相关， 可卡因DAT结构-功能关系分析（续） 在本财政年度，进一步描述了特定 非极性芳香族氨基酸在转运蛋白功能中的作用。这些研究 通过鉴定选择性结构-功能 可能在以下方面具有活性的先导候选小分子化合物的特征： 体内作为可卡因拮抗剂。 分析显示，候选人 对可卡因类似物识别具有显著选择性的化合物 与多巴胺摄取相比， 网站.这些化合物之一可以作为一个明显的部分可卡因 体内拮抗剂，阻断可卡因诱导的小鼠运动， 减少非人灵长类动物对可卡因的反应的断点 自我管理。

The dopamine transporter (DAT) has been identified as a principal brain receptor site correlated with the rewarding and euphoric properties of cocaine. Analyses of DAT structure-function relationships continued during this FY with further characterization of the roles of specific nonpolar aromatic amino acids in transporter function. These studies were supplemented by identification of selective structure-function features of lead candidate small molecule compounds possibly active in vivo as cocaine antagonists. These analyses revealed candidate compounds with significant selectivity for cocaine analog recognition compared with dopamine uptake and reduced cross-reactivity with other sites. One of these compounds can serve as an apparent partial cocaine antagonist in vivo, blocking cocaine-induced locomotion in mice and reducing the breakpoint of a non-human primate=s response for cocaine self-administration.