Evidence map›Paper›PMID 31743739›Full record

ArticleEuropean journal of pharmacology2019

Pharmacological characterization of 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-6-[(3'-fluoro-4'-pyridyl)acetamido]morphinan (NFP) as a dual selective MOR/KOR ligand with potential applications in treating opioid use disorder.

Yi Zheng, Samuel Obeng, Bethany A Reinecke, Chongguang Chen, Palak S Phansalkar, David M Walentiny, Phillip M Gerk, Lee-Yuan Liu-Chen, Dana E Selley, Patrick M Beardsley and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 46% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Yi ZhengDepartment of Medicinal Chemistry, Virginia Commonwealth University, 800 E. Leigh Street, Richmond, VA, 23298, United States.
Samuel ObengDepartment of Medicinal Chemistry, Virginia Commonwealth University, 800 E. Leigh Street, Richmond, VA, 23298, United States.
Bethany A ReineckeDepartment of Medicinal Chemistry, Virginia Commonwealth University, 800 E. Leigh Street, Richmond, VA, 23298, United States.
Chongguang ChenDepartment of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, United States.
Palak S PhansalkarDepartment of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA, 23298, United States.
David M WalentinyDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA, 23298, United States.
Phillip M GerkDepartment of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA, 23298, United States.
Lee-Yuan Liu-ChenDepartment of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, United States.
Dana E SelleyDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA, 23298, United States.
Patrick M BeardsleyDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA, 23298, United States; Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, 1112 East Clay Street, Richmond, VA, 23298, United States.
Yan ZhangDepartment of Medicinal Chemistry, Virginia Commonwealth University, 800 E. Leigh Street, Richmond, VA, 23298, United States. Electronic address: yzhang2@vcu.edu.
Virginia Commonwealth University · USTemple University · US

Funding

Pilot Projects Core (PPC)P30DA013429 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI Munir Gunes Kutlu · 2000 to 2026
$34.6M
Mu Opioid Receptor Modulator Development to Treat Opioid Use DisorderUH3DA050311 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2023 to 2025
$4.3M
Non-peptide Mu Opioid Receptor Selective AntagonistsR01DA024022 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2009 to 2019
$3.5M
Pharmacology of Kappa Opioid ReceptorR01DA041359 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI LIU-CHEN, LEE-YUAN · 2017 to 2021
$2.9M
Bivalent Ligands as Chemical Probes to Study Opioid Abuse-enhanced HIV InfectionR01DA044855 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F, ZHANG, YAN · 2017 to 2021
$2.7M
Novel fentanyl derivatives as counteracting agents against fentanylUG3DA050311 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2019 to 2020
$2.2M
Kappa opioid receptor in claustrumR21DA045274 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI LIU-CHEN, LEE-YUAN · 2018 to 2019
$436k
NIDA NIH HHS P30 DA013429NIDA NIH HHS R01 DA024022NIDA NIH HHS R01 DA041359NIDA NIH HHS R01 DA044855NIDA NIH HHS R21 DA045274NIDA NIH HHS UG3 DA050311NIDA NIH HHS UH3 DA050311
6 · The paper itself

Abstract

For thousands of years opioids have been the first-line treatment option for pain management. However, the tolerance and addiction potential of opioids limit their applications in clinic. NFP, a MOR/KOR dual-selective opioid antagonist, was identified as a ligand that significantly antagonized the antinociceptive effects of morphine with lesser withdrawal effects than naloxone at similar doses. To validate the potential application of NFP in opioid addiction treatment, a series of in vitro and in vivo assays were conducted to further characterize its pharmacological profile. In calcium mobilization assays and MOR internalization studies, NFP showed the apparent capacity to antagonize DAMGO-induced calcium flux and etorphine-induced MOR internalization. In contrast to the opioid agonists DAMGO and morphine, cells pretreated with NFP did not show apparent desensitization and down regulation of the MOR. Though in vitro bidirectional transport studies showed that NFP might be a P-gp substrate, in warm-water tail-withdrawal assays it was able to antagonize the antinociceptive effects of morphine indicating its potential central nervous system activity. Overall these results suggest that NFP is a promising dual selective opioid antagonist that may have the potential to be used therapeutically in opioid use disorder treatment.

Indexed as

Analgesics, OpioidAnimalsBiological TransportCaco-2 CellsCalciumCell Line, TumorCHO CellsCricetulusEnkephalin, Ala(2)-MePhe(4)-Gly(5)-HumansLigandsMaleMice, Inbred C57BLMorphinansNarcotic AntagonistsOpioid-Related DisordersAnalgesics, OpioidCalciumEnkephalin, Ala(2)-MePhe(4)-Gly(5)-LigandsMorphinansNarcotic AntagonistsReceptors, Opioid, kappaReceptors, Opioid, muDesensitizationDown regulationDrug abuse and addictionDual-selective opioid antagonistNFPOpioid use disorder

Identifiers

PMID31743739
PMCPMC6914219
OpenAlexW2986928262

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.