AFFINITY PROFILES OF MORPHINE, CODEINE, DIHYDROCODEINE AND THEIR GLUCURONIDES AT OPIOID RECEPTOR SUBTYPES
AFFINITY PROFILES OF MORPHINE, CODEINE, DIHYDROCODEINE AND THEIR GLUCURONIDES AT OPIOID RECEPTOR SUBTYPES
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DOI：
10.1016/0024-3205(95)00010-4
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发表时间：
1995-01-27
期刊：
影响因子：
6.1
通讯作者：
ZIEGLER, A
中科院分区：
文献类型：
--
作者：
MIGNAT, C;WILLE, U;ZIEGLER, A
研究了吗啡、可待因、二氢可待因及其葡萄糖醛酸苷对Mu-阿片受体、β-阿片受体和kappa-阿片受体的亲和力。研究了豚鼠脑匀浆与[H-3]DAMGO、[H-3]DPDPE和[H-3]U69593的结合作用。吗啡的自由酚基团的取代导致阿片受体结合的减少，但不影响Mu/Delta比率和Mu/kappa的比率。吗啡、可待因或二氢可待因的6-羟基葡醛酸化不影响与Mu受体的亲和力，略增加与Delta受体的亲和力，降低与kappa受体的亲和力。6-葡萄糖醛酸苷对Mu受体的选择性降低，而对Mu-Over kappa受体的选择性增加。结论：吗啡3位和6位的化学变化独立影响对阿片受体亚型的亲和力。
The affinity of morphine, codeine, dihydrocodeine and their glucuronides for mu-, delta-, and kappa-opioid receptors was investigated. Binding was studied on guinea-pig brain homogenates with [H-3]DAMGO, [H-3]DPDPE, and [H-3]U69593. The substitution of the free phenolic group of morphine caused a decrease in binding at opioid receptors without affecting the mu/delta ratio nor that of mu/kappa. Glucuronidation of the 6-hydroxyl group of morphine, codeine or dihydrocodeine did not affect the affinity to mu-receptors, slightly increased the affinity for delta-receptors and reduced the affinity for kappa-receptors. The 6-glucuronides possess a decreased selectivity for mu-receptors whereas that for mu- over kappa-receptors was increased. It is concluded that chemical variations at 3- and 6-position of morphine independently affect the affinity to opioid receptor subtypes.