CLINICAL ACTIONS OF FENTANYL AND BUPRENORPHINE - THE SIGNIFICANCE OF RECEPTOR-BINDING
CLINICAL ACTIONS OF FENTANYL AND BUPRENORPHINE - THE SIGNIFICANCE OF RECEPTOR-BINDING
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DOI：
10.1093/bja/57.2.192
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发表时间：
1985-01-01
影响因子：
9.8
通讯作者：
VILLIGER, JW
中科院分区：
文献类型：
--
作者：
BOAS, RA;VILLIGER, JW
[在大鼠中]进行受体结合试验，以阐明芬太尼和丁丙诺啡的阿片类药物结合特征，并研究它们之间的一些差异。丁丙诺啡表现出缓慢的受体结合（30分钟），但对多个位点具有高亲和力，从多个位点解离非常缓慢（T1/2[半衰期] = 166分钟）且不完全（1小时后结合50%）。这与芬太尼的受体结合形成对比，芬太尼的受体结合实现快速平衡（在10分钟内）并且同样快速（T1/2 = 6.8分钟）和完全（100%，1小时）解离。竞争性置换显示，在临床使用中遇到的范围内，芬太尼结合的丁丙诺啡置换是浓度和时间依赖性的，但丁丙诺啡结合仅被非常高浓度的其他阿片类药物置换。这些发现提供了芬太尼和丁丙诺啡镇痛反应谱差异的药效学解释，并表明如何将结合相互作用应用于治疗用途。
Receptor binding assays were undertaken [in rats] to elucidate the opioid binding characteristics of fentanyl and buprenorphine and to investigate some of the differences between them. Buprenorphine showed slow receptor association (30 min), but with high affinity to multiple sites from which dissociation was very slow (T1/2[half-life] = 166 min) and incomplete (50% binding after 1 h). This contrasted with the receptor binding of fentanyl, which achieved rapid equilibrium (within 10 min) and dissociated equally rapidly (T1/2 = 6.8 min) and completely (100% by 1 h). Competitive displacement showed buprenorphine displacement of fentanyl binding was concentration- and time-dependent over ranges encountered in clinical use, but buprenorphine binding was displaced with only very high concentrations of other opioids. These findings offer pharmacodynamic explanations for the differences in fentanyl and buprenorphine analgesic response profiles and suggest how binding interactions might be applied to therapeutic use.