吗啡和吗啡-6-葡萄糖醛酸苷不同毒性在阿片受体水平的解释。
Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide.
作者信息
Hucks D, Thompson P I, McLoughlin L, Joel S P, Patel N, Grossman A, Rees L H, Slevin M L
机构信息
Department of Chemical Endocrinology, St Bartholomew's Hospital, London, UK.
出版信息
Br J Cancer. 1992 Jan;65(1):122-6. doi: 10.1038/bjc.1992.23.
Abstract
The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu 1 or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained.
摘要
测定了吗啡及其活性代谢产物吗啡-6-葡萄糖醛酸苷对总μ受体、μ1受体、μ2受体和δ受体的放射性标记阿片受体结合亲和力。发现吗啡-6-葡萄糖醛酸苷对μ2受体的亲和力低4倍（吗啡和吗啡-6-葡萄糖醛酸苷的IC50分别为17 nM和82 nM，P = 0.01），该受体被认为是介导吗啡后呼吸抑制和胃肠道效应的原因。这为人类使用吗啡-6-葡萄糖醛酸苷后呼吸抑制和呕吐减少提供了一种可能的解释。在总μ受体上也观察到吗啡-6-葡萄糖醛酸苷亲和力有类似降低，而在μ1或δ受体上未观察到显著差异。因此，吗啡-6-葡萄糖醛酸苷比吗啡镇痛效力增强的原因仍无法解释。
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