| Title | 14beta-O-Cinnamoylnaltrexone and Related Dihydrocodeinones are Mu Opioid Receptor Partial Agonists with Predominant Antagonist Activity. | | Author(s) | Moynihan H, Jales AR, Greedy BM, Rennison D, Broadbear JH, Purington L, Traynor JR, Woods JH, Lewis JW, Husbands SM | | Institution | Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, U.K., School of Chemistry, University of Bristol, Bristol BS8 1TS, U.K., and Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109. | | Source | J Med Chem 2009 Mar 2. | | 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). | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19253983 |
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