14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity.

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Moynihan H, Jales AR, Greedy BM, Rennison D, Broadbear JH, Purington L, Traynor JR, Woods JH, Lewis JW, Husbands SM

14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity.

J Med Chem. 2009 Mar 26;52(6):1553-7. doi: 10.1021/jm8012272.

PubMed ID

19253983 [ View in PubMed

]

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).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Morphine	Kappa-type opioid receptor	EC 50 (nM)	484	N/A	N/A	Details
Morphine	Mu-type opioid receptor	EC 50 (nM)	15.6	N/A	N/A	Details