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Nanoconjugated NAP as a Potent and Periphery Selective Mu Opioid Receptor Modulator To Treat Opioid-Induced Constipation
journal contribution
posted on 2016-11-21, 00:00 authored by Guoyan
G. Xu, Olga Yu. Zolotarskaya, Dwight A. Williams, Yunyun Yuan, Dana E. Selley, William L. Dewey, Hamid I. Akbarali, Hu Yang, Yan ZhangOpioids are the mainstay for cancer
and noncancer pain management.
However, their use is often associated with multiple adverse effects.
Among them, the most common and persistent one is probably opioid-induced
constipation (OIC). Periphery selective opioid antagonists may alleviate
the symptoms of OIC without compromising the analgesic effects of
opioids. Recently our laboratories have identified one novel lead
compound, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4′-pyridyl)acetamido]morphinan
(NAP), as a peripherally selective mu opioid receptor ligand carrying
subnanomolar affinity to the mu opioid receptor and over 100-folds
of selectivity over both the delta and kappa opioid receptors, with
reasonable oral availability and half-life, and potential to treat
OIC. Nanoparticle-based drug delivery systems are now widely considered
due to their technological advantages such as good stability, high
carrier capacity, low therapeutic side effects, etc. Herein we report
nanoparticle supported NAP as a potential candidate for OIC treatment
with improved peripheral selectivity over the original lead compound
NAP.
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carrier capacityselectivityMu Opioid Receptor ModulatorPeripherykappa opioid receptorsNanoparticle-based drug delivery systemssubnanomolar affinityreport nanoparticleNanoconjugated NAPnoncancer pain managementOpioid-Induced Constipation OpioidsOIC treatmentopioid antagonistsopioid-induced constipationmu opioid receptor ligand100- foldsmu opioid receptorside effectscompound NAP
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