Comer Sandra D, Collins Eric D
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
J Pharmacol Exp Ther. 2002 Nov;303(2):695-703. doi: 10.1124/jpet.102.038141.
Buprenorphine is a partial mu-opioid agonist and kappa-opioid antagonist currently under development as a maintenance medication for heroin dependence. Because of concerns about illicit diversion of buprenorphine, a combination tablet containing buprenorphine and naloxone has been developed. The present study evaluated the reinforcing effects of intravenously administered placebo, buprenorphine alone (BUP; 2 and 8 mg), and the buprenorphine/naloxone combination (BUP/NX; 2 mg of buprenorphine plus 0.5 mg of naloxone, and 8 mg of buprenorphine plus 2 mg of naloxone) in recently detoxified heroin abusers during a 6-week inpatient study. Participants (n = 6) were detoxified from heroin over approximately 1 week immediately after admission. During the next 5 weeks, the reinforcing effects of placebo, BUP, and BUP/NX were evaluated. Participants first received a dose of drug and $20 and then were given the opportunity to self-administer either the dose or $20 during choice sessions. Progressive ratio break point values were significantly higher after active drug, compared with placebo, but they did not significantly differ as a function of dose or drug. In contrast, positive subjective ratings were higher after administration of BUP compared with BUP/NX, and these ratings increased in a dose-dependent manner. BUP and the combination had few effects on performance. Relative to placebo, both BUP and BUP/NX decreased pupil diameter, but there were no significant differences in pupil diameter as a function of drug or dose. These results demonstrate that both BUP and BUP/NX served as reinforcers under these conditions and that they may have similar abuse liability in recently detoxified individuals who abuse heroin.
丁丙诺啡是一种部分μ-阿片受体激动剂和κ-阿片受体拮抗剂，目前正作为海洛因依赖的维持药物进行研发。由于担心丁丙诺啡的非法转移，已开发出一种含有丁丙诺啡和纳洛酮的复方片剂。本研究在一项为期6周的住院研究中，评估了静脉注射安慰剂、单独的丁丙诺啡（BUP；2毫克和8毫克）以及丁丙诺啡/纳洛酮组合（BUP/NX；2毫克丁丙诺啡加0.5毫克纳洛酮，以及8毫克丁丙诺啡加2毫克纳洛酮）对近期戒毒的海洛因滥用者的强化作用。参与者（n = 6）入院后立即在大约1周内戒除海洛因。在接下来的5周内，评估安慰剂、BUP和BUP/NX的强化作用。参与者首先接受一剂药物和20美元，然后在选择环节中有机会自行给药或选择20美元。与安慰剂相比，活性药物给药后的渐进比率断点值显著更高，但它们并未因剂量或药物而有显著差异。相比之下，服用BUP后的积极主观评分高于BUP/NX，且这些评分呈剂量依赖性增加。BUP和组合对行为表现影响较小。相对于安慰剂，BUP和BUP/NX均降低了瞳孔直径，但瞳孔直径并未因药物或剂量而有显著差异。这些结果表明，在这些条件下，BUP和BUP/NX均起到了强化剂的作用，并且它们在近期戒毒的海洛因滥用个体中可能具有相似的滥用可能性。
