Strain E C, Preston K L, Liebson I A, Bigelow G E
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1992 Jun;261(3):985-93.
Buprenorphine is an opioid agonist-antagonist being evaluated for treatment of opioid dependence. This study characterized the effects of buprenorphine in comparison to naloxone, hydromorphone and saline, in methadone-dependent volunteers. In a residential laboratory, 6 volunteer male opioid abusers maintained on 30 mg of methadone daily underwent pharmacological challenges 2 to 3 times per week. Pharmacological challenges consisted of a double-blind i.m. injection of: buprenorphine (dose range 0.5-8.0 mg), hydromorphone (5 and 10 mg), naloxone (0.1 and 0.2 mg) or saline. Injections were given 20 hr after the last dose of methadone. Measures included physiologic indices, and self-report and observer ratings of drug effects. Naloxone and hydromorphone produced characteristic antagonist-like and agonist-like effects, respectively, on subjective, observer and physiologic indices. None of the doses of buprenorphine were consistently or systematically identified as an opioid agonist or antagonist on any of the measures. Thus buprenorphine produced minimal effects in methadone-dependent patients. The lack of agonist effects suggests buprenorphine has a low abuse potential in methadone-dependent patients. The lack of antagonist effects suggests buprenorphine can be administered safely to subjects dependent on a low dose of methadone. This lack of effect of buprenorphine distinguishes it from other mixed agonist antagonists previously tested, which produced antagonist effects in this procedure.
丁丙诺啡是一种正在接受评估用于治疗阿片类药物依赖的阿片类激动剂-拮抗剂。本研究比较了丁丙诺啡与纳洛酮、氢吗啡酮及生理盐水对美沙酮依赖志愿者的影响。在一个住院实验室中，6名每天服用30毫克美沙酮维持治疗的男性阿片类药物滥用志愿者，每周接受2至3次药理学激发试验。药理学激发试验包括双盲肌肉注射：丁丙诺啡（剂量范围0.5 - 8.0毫克）、氢吗啡酮（5毫克和10毫克）、纳洛酮（0.1毫克和0.2毫克）或生理盐水。注射在最后一剂美沙酮服用20小时后进行。测量指标包括生理指标，以及药物效应的自我报告和观察者评分。纳洛酮和氢吗啡酮分别对主观、观察者及生理指标产生了典型的拮抗剂样和激动剂样效应。在任何测量指标上，丁丙诺啡的任何剂量均未被一致或系统地鉴定为阿片类激动剂或拮抗剂。因此，丁丙诺啡在美沙酮依赖患者中产生的效应极小。缺乏激动剂效应表明丁丙诺啡在美沙酮依赖患者中的滥用潜力较低。缺乏拮抗剂效应表明丁丙诺啡可安全地给予依赖低剂量美沙酮的受试者。丁丙诺啡的这种无效性使其有别于先前测试的其他混合激动剂拮抗剂，后者在此程序中产生了拮抗剂效应。
