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. 1988 Aug;246(2):441-8.
The subjective, physiological and behavioral effects of hydromorphone, naloxone and butorphanol, an opioid agonist/antagonist analgesic, were studied in adult, male, methadone-dependent volunteers living on a clinical research ward. Drug conditions included saline placebo, 4 and 8 mg of hydromorphone HCl, 0.375, 0.75, 1.5, 3 and 6 mg of butorphanol tartrate and 0.1 and 0.2 mg of naloxone HCl. Drug conditions, given by i.m. injection, were tested in five subjects under double-blind conditions in 2.5-hr experimental sessions. Physiologic measures and subject- and observer-rated behavioral responses were measured before dosing and for 2 hr after drug administration. Hydromorphone decreased pupil diameter, and significantly increased ratings of "Good Effects" on the subjective measures. Naloxone precipitated opioid abstinence which was measurable on several subject- and observer-rated behavioral measures and physiological measures. Butorphanol produced effects which were generally similar to the effects of naloxone, indicating that butorphanol doses precipitate withdrawal signs and symptoms when administered to methadone-dependent humans. There were some differences in the withdrawal syndromes precipitated by naloxone vs. butorphanol, suggesting that multiple mechanisms may be involved in opioid withdrawal precipitation.
在临床研究病房生活的成年男性美沙酮依赖志愿者中，研究了氢吗啡酮、纳洛酮和阿片类激动剂/拮抗剂镇痛药布托啡诺的主观、生理和行为效应。药物条件包括生理盐水安慰剂、4毫克和8毫克盐酸氢吗啡酮、0.375毫克、0.75毫克、1.5毫克、3毫克和6毫克酒石酸布托啡诺以及0.1毫克和0.2毫克盐酸纳洛酮。通过肌肉注射给予的药物条件，在双盲条件下对五名受试者进行了2.5小时的实验测试。在给药前以及给药后2小时测量生理指标以及受试者和观察者评定的行为反应。氢吗啡酮可使瞳孔直径减小，并显著提高主观测量中“良好效果”的评分。纳洛酮引发阿片类药物戒断反应，这在受试者和观察者评定的多项行为指标和生理指标上均可测量。布托啡诺产生的效应通常与纳洛酮的效应相似，表明布托啡诺剂量在给予美沙酮依赖的人体时会引发戒断体征和症状。纳洛酮与布托啡诺引发的戒断综合征存在一些差异，这表明阿片类药物戒断反应的引发可能涉及多种机制。
