Evaluation of the cardiovascular and subjective effects of rivastigmine in combination with methamphetamine in methamphetamine-dependent human volunteers
Evaluation of the cardiovascular and subjective effects of rivastigmine in combination with methamphetamine in methamphetamine-dependent human volunteers
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DOI：
10.1017/s1461145708008456
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发表时间：
2008-09-01
影响因子：
4.8
通讯作者：
Newton, Thomas F.
中科院分区：
文献类型：
--
作者：
De La Garza, Richard, II;Shoptaw, Steve;Newton, Thomas F.
乙酰胆碱 (ACh) 与甲基苯丙胺 (Meth) 产生的强化和运动激活作用有关。有趣的是，最近的数据表明乙酰胆碱酯酶（AChE）抑制剂可以减弱大鼠的冰毒寻求行为。我们进行这项研究是为了确定 AChE 抑制剂卡巴拉汀 (Riv) 与冰毒联合使用时的安全性（不良事件、情绪变化、心血管影响）和初步疗效（主观效果）。 23 名未寻求治疗的冰毒依赖参与者在加州大学洛杉矶分校的住院部住了 2 周，并完成了这项双盲、受试者间、安慰剂对照研究。在随机分配研究药物之前，在 11:30 以单盲方式向所有参与者输注生理盐水（第 4 天，静脉注射 0 毫克）和冰毒（第 5 天，静脉注射 30 毫克）。从第 7 天一直持续到第 11 天，参与者被随机分配接受口服安慰剂（0 毫克，n=7）或 Riv（1.5 毫克，n=7；3 毫克，n=9）。第 11 天，受试者在双盲条件下再次接受盐水和冰毒输注（随机选择 11:30 或 14:30）。数据分析比较了不良事件和情绪的跨研究测量，以及心血管和主观影响的随机化后分析（第 11 天）。数据显示卡巴拉汀与不良事件增加或情绪改变无关。正如预期的那样，急性冰毒暴露（静脉注射 30 毫克）会增加心率和血压，以及一些积极的主观影响、成瘾研究中心清单 (ARCI) 评级和报告的货币价值 (p < 0.05)。数据表明，3 mg 的 Riv 显着减弱了冰毒引起的舒张压升高以及自我报告的“焦虑”和“欲望”（p < 0.05）。总而言之，本报告中的研究结果表明，增强大脑乙酰胆碱的药物操作值得继续研究，作为冰毒成瘾的潜在治疗方法。
Acetylcholine (ACh) has been implicated in the reinforcing and locomotor-activating effects produced by methamphetamine (Meth). Of interest, recent data suggest that acetylcholinesterase (AChE) inhibitors attenuate Meth-seeking behaviour in rats. We conducted this study in order to determine the safety (adverse events, mood changes, cardiovascular effects) and preliminary efficacy (subjective effects) of the AChE inhibitor rivastigmine (Riv) when tested in combination with Meth. Twenty-three non-treatment-seeking Meth-dependent participants resided in an in-patient unit at UCLA for 2 wk, and completed this double-blind, between-subjects, placebo-controlled study. Prior to randomization to study drug, infusions of saline (day 4, 0 mg i.v.) and Meth (day 5, 30 mg i.v.) were given to all participants at 11:30 hours in single-blinded fashion. On day 7 and continuing to day 11, participants were randomized to receive oral placebo (0 mg, n=7) or Riv, (1.5 mg, n=7; 3 mg, n=9). On day 11, the subjects received saline and Meth infusions again (randomized to either 11:30 or 14:30 hours), under double-blind conditions. The data analyses compared across-study measures of adverse events and mood, and a post-randomization analysis of cardiovascular and subjective effects (on day 11). The data reveal that rivastigmine was not associated with increased adverse events or alterations in mood. As expected, acute Meth exposure (30 mg i.v.) increased heart rate and blood pressure, as well as several positive subjective effects, Addiction Research Center Inventory (ARCI) ratings, and reported monetary value (p < 0.05). The data indicated that Riv, at 3 mg, significantly attenuated Meth-induced increases in diastolic blood pressure, and self-reports of 'anxious' and 'desire' (p < 0.05). Taken together, the findings in the current report Suggest that pharmacological manipulations that enhance brain ACh warrant continued investigation as potential treatments for Meth addiction.