Preston K L, Bigelow G E, Liebson I A
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1989 Mar;248(3):929-37.
The subjective, physiological and behavioral effects of nalbuphine, an opioid mixed agonist/antagonist analgesic, naloxone and hydromorphone were studied on adult, male, methadone-dependent volunteers living on a clinical research ward. The purpose was to assess nalbuphine's agonist properties vs. antagonist properties relative to a standard agonist (hydromorphone) and a standard antagonist (naloxone) in opioid-dependent subjects. Drug conditions included saline placebo, nalbuphine hydrochloride (0.375, 0.75, 1.5, 3 and 6 mg), naloxone hydrochloride (0.1 and 0.2 mg) and hydromorphone hydrochloride (4 and 8 mg). Drug conditions, given by i.m. injection, were tested in five subjects under double-blind conditions in 2.5 hr experimental sessions. Physiologic measures were monitored continuously before and for 2 hr after drug administration: pupil diameter and subject- and observer-rated behavioral responses were measured intermittently over this same period. Hydromorphone increased ratings significantly on subjective measures typical of morphine-like effects. Naloxone precipitated opioid abstinence which was measurable on several subject- and observer-rated behavioral measures and physiological measures. Nalbuphine produced effects which were qualitatively similar to the effects of naloxone and showed no evidence of opioid agonist effects in these methadone-dependent subjects. The withdrawal syndrome precipitated by nalbuphine was indistinguishable from that produced by naloxone.
在临床研究病房中，对成年男性美沙酮依赖志愿者研究了阿片类混合激动剂/拮抗剂镇痛药纳布啡、纳洛酮和氢吗啡酮的主观、生理及行为效应。目的是评估在阿片类药物依赖受试者中，相对于标准激动剂（氢吗啡酮）和标准拮抗剂（纳洛酮），纳布啡的激动剂特性与拮抗剂特性。药物条件包括生理盐水安慰剂、盐酸纳布啡（0.375、0.75、1.5、3和6毫克）、盐酸纳洛酮（0.1和0.2毫克）以及盐酸氢吗啡酮（4和8毫克）。通过肌肉注射给予的药物条件，在2.5小时的实验时段内，以双盲方式在五名受试者身上进行测试。给药前及给药后2小时持续监测生理指标：在此同一时期内间歇测量瞳孔直径以及受试者和观察者评定的行为反应。氢吗啡酮在典型的类吗啡效应主观指标上显著提高评分。纳洛酮引发阿片类戒断反应，这在多项受试者和观察者评定的行为指标及生理指标上均可测量。纳布啡产生的效应在性质上与纳洛酮的效应相似，并且在这些美沙酮依赖受试者中未显示出阿片类激动剂效应的证据。纳布啡引发的戒断综合征与纳洛酮引发的戒断综合征无法区分。
