Buprenorphine/naloxone reduces the reinforcing and subjective effects of heroin in heroin-dependent volunteers
Buprenorphine/naloxone reduces the reinforcing and subjective effects of heroin in heroin-dependent volunteers
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DOI：
10.1007/s00213-005-0023-6
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Collins, ED
中科院分区：
文献类型：
--
作者：
Comer, SD;Walker, EA;Collins, ED
理由：虽然丁丙诺啡对治疗阿片类药物依赖有效，但丁丙诺啡或丁丙诺啡/纳洛酮联合使用的最佳维持剂量尚未确定。目的：本研究旨在评价丁丙诺啡/纳洛酮维持（2/0.5、8/2、32/8 mg舌下）对海洛因依赖者（0、12.5、25、50、100 mg鼻内）强化和主观效应的影响。方法：在测试周，参与者（N=7）首先取样一剂海洛因和20美元。在随后的选择环节中，参与者可以选择自我管理海洛因和/或金钱。参与者在修改后的累进比率计划(PR 50，…（2,800），在十次自我管理任务中。结果：丁丙诺啡/纳洛酮8/2、32/8 mg组海洛因断点值和主观反应明显低于2/0.5 mg组。在丁丙诺啡/纳洛酮存在的情况下，海洛因的自我给药和主观效应数据与最近解毒的单独对照组（N=8）进行比较，以获得体内表观解离常数（K-A）、疗效估计（tau）和丁丙诺啡/纳洛酮治疗后剩余受体的估计分数(q)。海洛因的体内表观解离常数为50 ~ 126 mg (K-A)，药效估计为13 ~ 20 （tau）。此外，2/0.5、8/2和32/8 mg丁丙诺啡/纳洛酮的剂量依赖性分别使受体群体减少了74%、83%和91%。结论：与2/0.5 mg丁丙诺啡/纳洛酮相比，8/2 mg和32/8 mg丁丙诺啡/纳洛酮均具有良好的耐受性，可有效降低海洛因的强化效应和主观效应。该数据还首次在人类中表明，有可能量化海洛因对mu阿片受体的功效和亲和力，并且80-90%的mu受体需要灭活才能显著减少海洛因诱导的效应。这些结果对未来的研究具有重要意义，在这些研究中，将有可能获得不同激动剂对全阿片受体的相对亲和力和功效的估计。
Rationale: Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established. Objective: The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals. Methods: During test weeks, participants (N=7) first sampled a dose of heroin and $20. During subsequent choice sessions, participants could choose to self-administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50,..., 2,800) during a ten-trial self-administration task. Results: Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (K-A), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50 to 126 mg (K-A) and the efficacy estimate ranged from 13 to 20 (tau). In addition, 2/0.5, 8/2, and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74, 83, and 91%, respectively. Conclusions: These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5-mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors, and that 80-90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at Full opioid receptors.