Newton Thomas F, De La Garza Richard, Fong Tim, Chiang Nora, Holmes Tyson H, Bloch Daniel A, Anderson Ann, Elkashef Ahmed
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at The University of California at Los Angeles, USA.
Pharmacol Biochem Behav. 2005 Dec;82(4):704-11. doi: 10.1016/j.pbb.2005.11.012. Epub 2006 Jan 18.
Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor shown to be effective in the treatment of Parkinson's and Alzheimer's diseases. Recent evidence suggests that selegiline may also be useful in treating specific aspects of cocaine and nicotine dependence, generating interest in this compound for the treatment of methamphetamine addiction. To investigate this, we performed a randomized, single-blind, placebo-controlled study to evaluate the safety of selegiline treatment (as compared to placebo), concurrent with intravenous methamphetamine (15 or 30 mg). Secondary study objectives included determinations of plasma levels of selegiline and its metabolites, evaluating whether selegiline administration altered the pharmacokinetics of methamphetamine or its metabolites, and evaluating whether selegiline treatment alters the subjective responses to methamphetamine. Twenty-four methamphetamine-dependent participants were randomized to treatment, and 9 of these (N = 5 selegiline, N = 4 placebo) completed the entire protocol. The principal finding from this study was that intravenous administration of moderate doses of methamphetamine was safely tolerated during treatment with selegiline. No participants had electrocardiogram changes, and there were no meaningful differences in any laboratory values either between groups at screening or as a result of the study procedures. In general, adverse events were mild or moderate, and no subjects were discontinued due to adverse events or serious adverse events. Selegiline treatment did not enhance any of the cardiovascular changes (heart rate, blood pressure) produced by methamphetamine administration. Selegiline treatment slightly increased methamphetamine associated "bad effects" but did not alter any other subjective effects. The elimination half-life of methamphetamine was approximately 12 h, and selegiline did not alter clearance of methamphetamine. The available data suggest that selegiline is likely to be safe if used as a pharmacotherapy for methamphetamine dependence.
司来吉兰（L-司来吉兰）是一种选择性不可逆单胺氧化酶B抑制剂，已被证明对帕金森病和阿尔茨海默病的治疗有效。最近的证据表明，司来吉兰可能也有助于治疗可卡因和尼古丁依赖的特定方面，这引发了人们对该化合物治疗甲基苯丙胺成瘾的兴趣。为了对此进行研究，我们开展了一项随机、单盲、安慰剂对照研究，以评估司来吉兰治疗（与安慰剂相比）的安全性，同时静脉注射甲基苯丙胺（15或30毫克）。次要研究目标包括测定司来吉兰及其代谢物的血浆水平，评估司来吉兰给药是否改变甲基苯丙胺或其代谢物的药代动力学，以及评估司来吉兰治疗是否改变对甲基苯丙胺的主观反应。24名甲基苯丙胺依赖参与者被随机分组接受治疗，其中9名（N = 5司来吉兰组，N = 4安慰剂组）完成了整个方案。这项研究的主要发现是，在司来吉兰治疗期间，静脉注射中等剂量的甲基苯丙胺可安全耐受。没有参与者出现心电图变化，在筛查时或研究过程后，两组之间的任何实验室值均无显著差异。总体而言，不良事件为轻度或中度，没有受试者因不良事件或严重不良事件而停药。司来吉兰治疗并未增强甲基苯丙胺给药所产生的任何心血管变化（心率、血压）。司来吉兰治疗略微增加了与甲基苯丙胺相关的“不良影响”，但未改变任何其他主观影响。甲基苯丙胺的消除半衰期约为12小时，司来吉兰未改变甲基苯丙胺的清除率。现有数据表明，司来吉兰用作甲基苯丙胺依赖的药物治疗可能是安全的。
