Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.
Synthesis and pharmacologic characterization of an alkylating analogue (chlornaltrexamine) of naltrexone with ultralong-lasting narcotic antagonist properties.
复制标题
具有超长效麻醉拮抗剂特性的纳曲酮烷基化类似物（氯醛曲明）的合成和药理学表征。
DOI：
10.1021/jm00188a008
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发表时间：
1979
影响因子：
7.3
通讯作者：
A. Takemori
中科院分区：
文献类型：
--
作者：
P. Portoghese;D. L. Larson;J. B. Jiang;T. P. Caruso;A. Takemori
氯那曲胺（CNA）在小鼠中产生超长时间（3- 6天）的麻醉拮抗作用，并与大鼠脑匀浆产生持久的立体特异性结合。小鼠保护研究表明，CNA通过与纳洛酮占据的相同受体相互作用来介导其麻醉拮抗剂作用。单icv剂量的CNA也被发现可以抑制小鼠身体依赖的发展至少3天。这些研究表明，CNA通过与阿片受体的选择性共价结合发挥其持续作用。
Chlornaltrexamine (CNA) produces ultralong-lasting (3--6 days) narcotic antagonism in mice and persistent stereospecific binding to rat-brain homogenate. Protection studies in mice suggest that CNA mediates its narcotic antagonist effects by interacting with the same receptors that are occupied by naloxone. A single icv dose of CNA also has been found to inhibit the development of physical dependence in mice for at least 3 days. These studies suggest that CNA exerts its sustained effects by selective covalent association with opioid receptors.