BUPRENORPHINE - DEMONSTRATION OF PHYSICAL-DEPENDENCE LIABILITY
BUPRENORPHINE - DEMONSTRATION OF PHYSICAL-DEPENDENCE LIABILITY
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DOI：
10.1016/0014-2999(81)90163-1
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发表时间：
1981-01-01
影响因子：
5
通讯作者：
HERZ, A
中科院分区：
文献类型：
--
作者：
DUM, J;BLASIG, J;HERZ, A
本研究旨在评估阿片部分激动剂丁丙诺啡的依赖性产生能力。用丁丙诺啡长期处理4天的大鼠在停止丁丙诺啡处理或用纳洛酮激发后仅显示出非常弱的戒断体征，但此时对药物产生了完全耐受性。当丁丙诺啡治疗后用吗啡替代治疗时，可以诱导更强烈的戒断。即使在最后一次丁丙诺啡治疗后12小时注射1次吗啡，也可以用纳洛酮沉淀戒断。纳洛酮不能沉淀与此剂量的吗啡处理的幼稚大鼠戒断的迹象。丁丙诺啡，像其他阿片激动剂和部分激动剂，诱导依赖性。在直接依赖性试验中仅观察到少量戒断症状，这可能反映了药物与受体的缓慢解离，这可能通过阻止在药物治疗停止或注射拮抗剂时受体的快速分解来限制戒断强度。此外，与纯激动剂相比，丁丙诺啡诱导的最大依赖程度有限，与其他部分激动剂相似。
This study was designed to assess the dependence-producing capacity of the opiate partial agonist, buprenorphine. Rats chronically treated with buprenorphine for 4 days showed only very weak signs of withdrawal upon cessation of buprenorphine treatment or upon challenge with naloxone, but complete tolerance had developed to the drug at this time. More intense withdrawal could be induced when buprenorphine treatment was followed by substitution treatment with morphine. Even 1 injection of morphine given 12 h after the last buprenorphine treatment enabled the precipitation of withdrawal with naloxone. Naloxone could not precipitate signs of withdrawal in naive rats treated with this dose of morphine. Buprenorphine, like other opiate agonists and partial agonists, induces dependence. The fact that only few signs of withdrawal are seen in direct dependence tests, probably reflects the slow dissociation of the drug from the receptor, which probably limits the intensity of withdrawal by preventing the rapid uncovery of the receptor upon discontinuance of treatment with the drug or upon injection of an antagonist. In addition, the maximum degree of dependence induced by buprenorphine, in comparison to pure agonists, is limited, like that of other partial agonists.