Houtsmuller E J, Walsh S L, Schuh K J, Johnson R E, Stitzer M L, Bigelow G E
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Pharmacol Exp Ther. 1998 May;285(2):387-96.
Levo-alpha-acetylmethadol (LAAM) currently is approved as an opioid maintenance treatment. This double-blind study was designed to characterize withdrawal suppression and opioid blockade produced by two different LAAM maintenance doses. Outpatient opioid-dependent volunteers were stabilized (5-7 weeks) on 25 (n = 8) or 75 mg (n = 8) LAAM administered every-other-day with placebo administered on intervening days. After stabilization, four inpatient, randomly ordered experimental sessions were conducted at 24, 48, 72 and 96 hr after LAAM dosing; the timing of these sessions corresponds to intervals that occur during typical thrice-weekly treatment and after a missed dose. During each session, after baseline assessments, ascending doses of hydromorphone (0, 6 and 12 mg i.m.) were administered 45 min apart; physiological, subjective and observer-rated effects were recorded throughout the session. Physiological and subjective indices of opioid withdrawal measured at session base lines increased with time since the last LAAM dose, but did not depend on the maintenance dose. Withdrawal symptoms were mild in both groups, even at 96 hr after LAAM dosing. Hydromorphone produced dose-related opioid agonist effects at all intervals in the 25 mg LAAM group; these effects were attenuated substantially in the 75 mg LAAM group. Time since last LAAM dose had little influence on hydromorphone effects in either group. Thus, 75 mg LAAM provides opioid blockade and withdrawal suppression for up to 96 hr, whereas 25 mg LAAM is relatively ineffective at producing significant opioid blockade.
左旋 -α- 乙酰美沙朵（LAAM）目前被批准用于阿片类药物维持治疗。这项双盲研究旨在描述两种不同LAAM维持剂量产生的戒断抑制和阿片类药物阻断作用。门诊阿片类药物依赖志愿者分别服用25毫克（n = 8）或75毫克（n = 8）的LAAM，隔天给药，中间日服用安慰剂，持续5 - 7周以达到稳定状态。稳定期后，在LAAM给药后24、48、72和96小时进行了四次住院的随机顺序实验；这些实验时间对应于典型的每周三次治疗期间以及漏服一剂后的间隔时间。在每次实验中，基线评估后，每隔45分钟静脉注射递增剂量的氢吗啡酮（0、6和12毫克）；在整个实验过程中记录生理、主观和观察者评定的效果。实验基线时测量的阿片类药物戒断的生理和主观指标随自上次LAAM给药后的时间增加，但不依赖于维持剂量。两组的戒断症状都很轻微，即使在LAAM给药后96小时也是如此。在25毫克LAAM组中，氢吗啡酮在所有时间间隔都产生了剂量相关的阿片类激动剂效应；在75毫克LAAM组中，这些效应显著减弱。自上次LAAM给药后的时间对两组中氢吗啡酮的效应影响很小。因此，75毫克LAAM可提供长达96小时的阿片类药物阻断和戒断抑制作用，而25毫克LAAM在产生显著的阿片类药物阻断方面相对无效。
