期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 494, 期 2-3, 页码 121-130出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2004.04.050
关键词
delta opioid receptor; mu opioid receptor; kappa opioid receptor; inverse agonist
Differences in the anorectic activity of morphinan (e.g., naltrexone) and 3,4-dimethyl-4-(3 -hydroxyphenyl)piperidine (4PP) opioid receptor antagonists have been described. In an attempt to explain these differences, the influence of Na+ on opioid binding affinity and functional activity of 4PP antagonists was compared to other opioid antagonists. The binding affinities of neutral antagonists were unaffected by the addition of Na+, whereas that for the peptide, inverse agonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI174864) was increased. Similarly, the binding affinities of the 4PP antagonist (3R,4R)-1-((S)-3-hydroxy-3-cyclohexylpropyl)-4-(3-hydroxyphenyi)-3,4-dimethyl-1-piperidine (LY255582) and other 4PP antagonists were increased in the presence of Na+ with the greatest effects at the delta opioid receptor followed by the mu and kappa opioid receptors, respectively. Similar to ICI174864, 4PP antagonists were found to inhibit basal GTPgamma[S-35] binding at the delta opioid receptor indicating inverse agonist activity. A correlation was observed between the binding affinities in the presence of Na+, the inverse agonist potency, and the anorectic potency of 4PP antagonists. These data suggest that 4PP antagonists differ from morphinan antagonists in their inverse agonist activity and suggest a relationship between inverse agonism and anorectic activity. (C) 2004 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据