Title

Nanoconjugated NAP as a Potent and Periphery Selective Mu Opioid Receptor Modulator to Treat Opioid-Induced Constipation

Abstract

Opioids 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-3,14ß-dihydroxy-4,5α-epoxy-6ß-[(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.

Department(s)

Chemical and Biochemical Engineering

Keywords and Phrases

Mu opioid receptor antagonist; Nanoconjugate; NAP; Opioid-induced constipation; Periphery selective

International Standard Serial Number (ISSN)

1948-5875

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2017 American Chemical Society (ACS), All rights reserved.

Publication Date

21 Nov 2017

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