14-β-O-肉桂酰纳曲酮及相关二氢可待因酮是μ阿片受体部分激动剂，具有主要的拮抗剂活性。
14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity.
作者信息
Moynihan H, Jales A R, Greedy B M, Rennison D, Broadbear J H, Purington L, Traynor J R, Woods J H, Lewis J W, Husbands S M
机构信息
Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
出版信息
J Med Chem. 2009 Mar 26;52(6):1553-7. doi: 10.1021/jm8012272.
Abstract
14-O-Cinnamoyl esters of naltrexone (6) were synthesized and evaluated in isolated tissue assays in vitro and in vivo in mouse antinociceptive assays. Their predominant opioid receptor activity was mu receptor (MOR) antagonism, but the unsubstituted cinnamoyl derivative (6a) had partial MOR agonist activity in vitro and in vivo. When compared to the equivalent 14-cinnamoylaminomorphinones (5), the cinnamoyloxy morphinones (6) as MOR antagonists had a shorter duration of action and were less effective as pseudoirreversible antagonists. The antinociceptive activity of the cinnamoyloxycodeinones (7) was not significantly greater than that of the morphinones (6), but they exhibited no evidence of any pseudoirreversible MOR antagonism. In both respects, these profiles differed from those of the equivalent 14-cinnamoylaminocodeinones (4).
摘要
合成了纳曲酮（6）的14 - O - 肉桂酰酯，并在体外分离组织试验和小鼠体内抗伤害感受试验中进行了评估。它们主要的阿片受体活性是μ受体（MOR）拮抗作用，但未取代的肉桂酰衍生物（6a）在体外和体内具有部分MOR激动剂活性。与等效的14 - 肉桂酰氨基吗啡酮（5）相比，作为MOR拮抗剂的肉桂酰氧基吗啡酮（6）作用持续时间较短，作为假不可逆拮抗剂的效果较差。肉桂酰氧基可待因酮（7）的抗伤害感受活性并不显著高于吗啡酮（6），但它们没有表现出任何假不可逆MOR拮抗作用的证据。在这两个方面，这些特征与等效的14 - 肉桂酰氨基可待因酮（4）不同。
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