Greenwald M K, Stitzer M L
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 48207, USA.
Drug Alcohol Depend. 1998 Dec 1;53(1):17-30. doi: 10.1016/s0376-8716(98)00104-5.
This study compared the direct effects and acute physical dependence of butorphanol and morphine, opioids with differing actions at mu versus kappa receptors. Six non-dependent heroin-using volunteers were exposed to six conditions in a within-subject, Latin square design using double-blind procedures. In each session, agonist effects of single i.m. injections of butorphanol (3 and 6 mg/70 kg), morphine (15 and 30 mg/70 kg), lorazepam (4 mg/70 kg) or saline were evaluated. Butorphanol and morphine produced effects of comparable magnitude on miosis and reports of 'any drug effect'. Volunteers reported dysphoria, confusion and sedation after butorphanol, subjective effects that overlapped with those of lorazepam, whereas morphine produced euphoria and stimulation. Acute physical dependence (i.e. precipitated withdrawal responses to naloxone 10 mg/70 kg i.m. administered 6 h after each treatment) significantly increased after 30 mg/70 kg morphine but not after butorphanol treatments. These differences in naloxone sensitivity are likely due to differences in opioid receptor (mu versus kappa) activity, affinity and efficacy of these compounds. Pharmacological ramifications of these results are discussed.
本研究比较了布托啡诺和吗啡的直接作用及急性身体依赖性，这两种阿片类药物对μ受体和κ受体的作用不同。采用双盲程序，在一项受试者自身的拉丁方设计中，让6名无依赖性的海洛因使用者志愿者暴露于六种条件下。在每次实验中，评估单次肌肉注射布托啡诺（3毫克/70千克和6毫克/70千克）、吗啡（15毫克/70千克和30毫克/70千克）、劳拉西泮（4毫克/70千克）或生理盐水的激动剂效应。布托啡诺和吗啡对瞳孔缩小及“任何药物效应”的报告产生的效应程度相当。志愿者在使用布托啡诺后报告有烦躁不安、意识模糊和镇静作用，这些主观效应与劳拉西泮的效应重叠，而吗啡则产生欣快感和兴奋作用。在接受30毫克/70千克吗啡治疗后，急性身体依赖性（即每种治疗后6小时肌肉注射10毫克/70千克纳洛酮引发的戒断反应）显著增加，而布托啡诺治疗后则未增加。纳洛酮敏感性的这些差异可能是由于这些化合物在阿片受体（μ受体与κ受体）活性、亲和力和效能方面存在差异。讨论了这些结果的药理学意义。
