Rosen M I, McMahon T J, Hameedi F A, Pearsall H R, Woods S W, Kreek M J, Kosten T R
Connecticut Mental Health Center, New Haven, USA.
J Pharmacol Exp Ther. 1996 Mar;276(3):1128-35.
The purpose of this pilot study was to validate a methodology for testing the opioid withdrawal-attenuating effects of new medications using clonidine as a positive control. Seven heroin-dependent subjects stabilized on levorphanol received naloxone challenge tests on 4 consecutive days in a 2 x 2 design with placebo or clonidine (0.4-0.5 mg) pretreatment, followed by 0.2 or 0.4 mg of i.v. naloxone. The change in the area-under-the-curve from the preclonidine base line for various measures of withdrawal was analyzed in a two-factor (naloxone dose and clonidine condition) analysis of variance. Clonidine significantly (P < .05) attenuated systolic and diastolic blood pressure, pulse, lacrimation, nasal congestion and plasma cortisol, but not subject-rated withdrawal severity. There was a robust dose-dependent adrenocorticotropic hormone response to naloxone that was not changed by clonidine pretreatment. The consistency between these results and prior studies of clonidine's antiwithdrawal efficacy suggests the validity of the methodology for testing medications to treat opiate withdrawal. Studies with larger samples are needed to refine this methodology.
这项初步研究的目的是验证一种使用可乐定作为阳性对照来测试新药阿片类药物戒断缓解作用的方法。七名依赖左旋吗啡酮且病情稳定的海洛因依赖者，按照2×2设计，在连续4天接受纳洛酮激发试验，试验前分别给予安慰剂或可乐定（0.4 - 0.5毫克）预处理，随后静脉注射0.2毫克或0.4毫克纳洛酮。在双因素（纳洛酮剂量和可乐定条件）方差分析中，分析了可乐定预处理前基线水平与各种戒断指标曲线下面积的变化。可乐定显著（P < 0.05）降低了收缩压、舒张压、脉搏、流泪、鼻充血和血浆皮质醇，但对受试者评定的戒断严重程度没有影响。对纳洛酮有强烈的剂量依赖性促肾上腺皮质激素反应，可乐定预处理对此没有改变。这些结果与之前关于可乐定抗戒断疗效研究的一致性表明，该测试治疗阿片类药物戒断药物的方法是有效的。需要更大样本量的研究来完善该方法。
