Cornish James W, Herman Barbara H, Ehrman Ronald N, Robbins Steven J, Childress Anna Rose, Bead Valerani, Esmonde Catherine A, Martz Karen, Poole Sabrina, Caruso Frank S, O'Brien Charles P
Veteran's Affairs Medical Center, University & Woodland Aves., Philadelphia, PA 19104, USA.
Drug Alcohol Depend. 2002 Jul 1;67(2):177-83. doi: 10.1016/s0376-8716(02)00025-x.
The NMDA antagonist dextromethorphan hydrobromide (DM) may be useful in the treatment of opioid dependence, particularly as a means of reducing tolerance to methadone during replacement therapy. As a prelude to clinical efficacy studies, a randomized, double-blind, placebo-controlled study examined the safety of DM in combination with methadone in inpatient, opiate-dependent volunteers. Male participants received daily methadone (50-70 mg/day) and either DM (n=10) or placebo (n=5) during the 12-day active medication phase of the study. DM participants received doses of 120, 240, and 480 mg/day in increasing order (4 days each). DM at high doses caused mild elevations of heart rate, blood pressure, temperature, and plasma bromide. However, none of these effects was clinically significant. DM caused no significant changes in respiration, pupil diameter, or subjective drug effects measured by standard scales. Participants in the DM group reported many more adverse events than did subjects on placebo (173 vs. 21), but these effects were not clinically serious. The most commonly reported side effects were sleepiness and drowsiness. Several participants reported intoxicating effects at the highest dose. Overall, DM was well-tolerated by the methadone-maintained opiate-dependent subjects studied here. These results support the further exploration of DM as an adjunct medication during methadone replacement therapy.
N-甲基-D-天冬氨酸（NMDA）拮抗剂氢溴酸右美沙芬（DM）可能有助于治疗阿片类药物依赖，尤其是作为在替代疗法期间降低对美沙酮耐受性的一种手段。作为临床疗效研究的前奏，一项随机、双盲、安慰剂对照研究在住院的阿片类药物依赖志愿者中考察了DM与美沙酮联合使用的安全性。在该研究为期12天的活性药物治疗阶段，男性参与者每日服用美沙酮（50 - 70毫克/天），并分别服用DM（n = 10）或安慰剂（n = 5）。服用DM的参与者按递增顺序每日分别服用120、240和480毫克（各服用4天）。高剂量的DM导致心率、血压、体温和血浆溴轻度升高。然而，这些影响在临床上均不显著。DM对呼吸、瞳孔直径或通过标准量表测量的主观药物效应均无显著影响。DM组的参与者报告的不良事件比服用安慰剂的受试者多得多（173起对21起），但这些影响在临床上并不严重。最常报告的副作用是嗜睡和困倦。几名参与者报告在最高剂量时有中毒效应。总体而言，本文研究的美沙酮维持治疗的阿片类药物依赖受试者对DM耐受性良好。这些结果支持进一步探索将DM作为美沙酮替代疗法期间的辅助药物。
