Rothman Richard B, Baumann Michael H, Prisinzano Thomas E, Newman Amy Hauck
Clinical Psychopharmacology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 333 Cassell Dr., Baltimore, MD 21224, USA.
Biochem Pharmacol. 2008 Jan 1;75(1):2-16. doi: 10.1016/j.bcp.2007.08.007. Epub 2007 Aug 9.
The discovery and development of medications to treat addiction and notably, cocaine addiction, have been frustrated by both the complexity of the disorder and the lack of target validation in human subjects. The dopamine transporter has historically been a primary target for cocaine abuse medication development, but addictive liability and other confounds of such inhibitors of dopamine uptake have limited clinical evaluation and validation. Herein we describe efforts to develop analogues of the dopamine uptake inhibitors GBR 12909 and benztropine that show promising profiles in animal models of cocaine abuse that contrast to that of cocaine. Their unique pharmacological profiles have provided important insights into the reinforcing actions of cocaine and we propose that clinical investigation of novel dopamine uptake inhibitors will facilitate the discovery of cocaine-abuse medications.
用于治疗成瘾，尤其是可卡因成瘾的药物的发现和开发，一直因该疾病的复杂性以及人体受试者中缺乏靶点验证而受阻。多巴胺转运体在历史上一直是可卡因滥用药物开发的主要靶点，但此类多巴胺摄取抑制剂的成瘾性及其他混杂因素限制了临床评估和验证。在此我们描述了开发多巴胺摄取抑制剂GBR 12909和苯海索类似物的努力，这些类似物在可卡因滥用动物模型中显示出与可卡因不同的有前景的特征。它们独特的药理特性为可卡因的强化作用提供了重要见解，我们提出对新型多巴胺摄取抑制剂的临床研究将有助于发现可卡因滥用药物。
