Administrative and Scientific Core

这个药物开发中心(MDU)的主题是开发新的GABA增强 药物和使用遗传方法来最佳匹配成功的可卡因药物疗法，如 AS双硫兰和GABA再摄取阻滞剂替加宾用于可卡因依赖患者的亚组。我们是 进行两项门诊随机临床试验和一系列五项实验室筛选研究 GABA增强剂。项目1是一项随机、安慰剂对照、为期12周的临床试验，检查150 双硫仑和GABA再摄取阻滞剂在可卡因依赖美沙酮稳定患者中的应用 替加宾。这些患者将根据功能性多巴胺β羟基酶(DBH)进行分层。 基因多态与预测双硫兰治疗反应的关系 导致低胸径水平和相对较高的多巴胺(DA)水平的单倍型。项目2包括140 一项为期12周的随机、安慰剂对照的抑郁症、近期戒断、可卡因依赖患者的研究 四个治疗组的复发试验：安慰剂、舍曲林、舍曲林+替加宾和舍曲林+舍曲林 加巴喷丁。这项试验包括最初两周的住院禁欲。方案1和方案1中的患者 2将接受GABA相关基因多态的遗传筛选，作为潜在的治疗预测因素 在未来的研究中对GABA增强剂的反应。项目3将使用可卡因给人类在一个 实验室，以筛选五种GABA增强剂作为药物治疗的潜在效用。这些 三个项目涉及在临床试验中检查九种不同的潜在可卡因药物疗法和 人体实验室。这些临床试验在双硫兰增强DA方面提供了一个有趣的对比。 多巴胺再摄取阻滞剂舍曲林与GABA增强剂--替加宾和加巴喷丁减少多巴胺的比较。 总体而言，该中心将对300多名患者进行研究，并在两个门诊第二阶段对8种不同的药物进行研究 试验或人体实验室研究。

This Center for Medications Development (MDU) has a theme of developing new GABA enhancing medications and using genetic approaches to optimally match successful cocaine pharmacotherapies such as disulfiram and the GABA reuptake blocker tiagabine to subgroups of cocaine dependent patients. We are conducting two outpatient randomized clinical trials and a series of five laboratory screening studies for new GABA enhancers. Project 1 is a randomized, placebo-controlled, 12-week clinical trial examining 150 cocaine-dependent methadone-stabilized patients in a trial of disulfiram and the GABA reuptake blocker tiagabine. These patients will be stratified based on a functional dopamine beta hydroxylase (DBH) polymorphism with the prediction of a treatment response to disulfiram only in those with the genetic haplotype that leads to low DBH levels and relatively higher dopamine (DA) levels. Project 2 includes 140 depressed, recently abstinent, cocaine-dependent patients in a randomized, placebo-controlled, 12-week relapse trial with four treatment groups: placebo, sertraline, sertraline + tiagabine and sertraline + gabapentin. This trial includes an initial 2 weeks of inpatient abstinence. The patients in both Projects 1 and 2 will undergo genetic screening of GABA related polymorphisms as potential predictors of treatment response to GABA enhancers in future studies. Project 3 will use cocaine administration to humans in a laboratory in order to screen five GABA enhancers for their potential utility as pharmacotherapies. These three projects involve examination of nine different potential cocaine pharmacotherapies in clinical trials and the human laboratory. These clinical trials offer an interesting contrast in DA enhancement by disulfiram .or the DA reuptake blocker sertraline versus DA reduction by the GABA enhancers - tiagabine and gabapentin. Overall, over 300 patients will be studied in this Center and eight different agents in either outpatient Phase II trials or human laboratory studies.