INVIVO RECEPTOR-BINDING OF THE OPIATE PARTIAL AGONIST, BUPRENORPHINE, CORRELATED WITH ITS AGONISTIC AND ANTAGONISTIC ACTIONS
INVIVO RECEPTOR-BINDING OF THE OPIATE PARTIAL AGONIST, BUPRENORPHINE, CORRELATED WITH ITS AGONISTIC AND ANTAGONISTIC ACTIONS
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DOI：
10.1111/j.1476-5381.1981.tb10473.x
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发表时间：
1981-01-01
影响因子：
7.3
通讯作者：
HERZ, A
中科院分区：
文献类型：
--
作者：
DUM, JE;HERZ, A
1为了更深入地了解阿片类部分激动剂背后的作用机制，结合大鼠对药物的活体结合研究，对部分激动剂丁丙诺啡的双重激动剂/拮抗剂特性进行了分析。2丁丙诺啡显示抗伤害作用的剂量-反应曲线呈钟形曲线，峰值约为2.00。皮下注射0.5 mg/kg。它在正常具有激活性的剂量下拮抗吗啡的抗伤害作用，在高于显著激活性的剂量时产生最大的拮抗作用。在高度吗啡依赖的大鼠中，丁丙诺啡的催促戒断能力在高于激动剂活性的剂量下存在。丁丙诺啡的整个剂量-反应曲线被阿片拮抗剂纳曲酮对称右移。3丁丙诺啡对活体受体的剂量依赖性占据似乎在激动剂剂量范围内几乎完全，在拮抗剂范围内几乎没有进一步的受体占据。4讨论了点对点受体相互作用导致效应的协同性的可能性。
1In order to gain more insight into the mechanisms behind the actions of opiate partial agonists, an analysis of the dual agonist/antagonist properties of the partial agonist, buprenorphine, was made in conjunction within vivobinding studies of the drug in the rat.2Buprenorphine revealed a bell‐shaped dose‐response curve for antinociception peaking at approx. 0.5 mg/kg subcutaneously. It antagonized morphine antinociception at doses which normally have agonistic effects and produced maximum antagonistic effects at doses above those having prominent agonistic activity. The withdrawal precipitating potency of buprenorphine as measured in highly morphine‐dependent rats was present at doses above those having agonistic activity. The entire dose‐response curve for buprenorphine was shifted symmetrically to the right by the opiate antagonist, naltrexone.3The dose‐dependent occupation of receptorsin vivoby buprenorphine seemed to be almost complete over the agonist dosage range; almost no further receptor occupation over the antagonist range was seen.4The possibility is discussed that site‐to‐site receptor interactions leading to cooperativity of effect may be the best explanation of these results.