Evidence map›Paper›PMID 24815322›Full record

ArticleEuropean journal of pharmacology2014

Behavioral and cellular pharmacology characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan (NAQ) as a mu opioid receptor selective ligand.

Yan Zhang, Amanda Braithwaite, Yunyun Yuan, John M Streicher, Edward J Bilsky

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Yan ZhangDepartment of Medicinal Chemistry, Virginia Commonwealth University, 800 East Leigh Street, P.O. Box 980540, Richmond, VA 23298, United States. Electronic address: yzhang2@vcu.edu.
Amanda BraithwaiteDepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, 11 Hills Beach Road, Biddeford, ME 04005, United States.
Yunyun YuanDepartment of Medicinal Chemistry, Virginia Commonwealth University, 800 East Leigh Street, P.O. Box 980540, Richmond, VA 23298, United States.
John M StreicherDepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, 11 Hills Beach Road, Biddeford, ME 04005, United States.
Edward J BilskyDepartment of Biomedical Sciences, College of Osteopathic Medicine, University of New England, 11 Hills Beach Road, Biddeford, ME 04005, United States.
University of New England · USVirginia Commonwealth University · US

Funding

Non-peptide Mu Opioid Receptor Selective AntagonistsR01DA024022 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2009 to 2019
$3.5M
NIDA NIH HHS DA024022NIDA NIH HHS R01 DA024022
6 · The paper itself

Abstract

Mu opioid receptor (MOR) selective antagonists and partial agonists have been used for the treatment of opioid abuse and addiction. Our recent efforts on the identification of MOR antagonists have provided several novel leads displaying interesting pharmacological profiles. Among them, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-[(3'-isoquinolyl)acetamido]morphinan (NAQ) showed sub-nanomolar binding affinity to the MOR with significant selectivity over the delta opioid receptor (DOR) and the kappa opioid receptor (KOR). Its central nervous system penetration capacity together with marginal agonism in the MOR-GTPγS binding assay made it a very interesting molecule for developing novel opioid abuse and addiction therapeutic agents. Therefore, further pharmacological characterization was conducted to fully understand its biological profile. At the molecular and cellular level, NAQ not only induced no translocation of β-arrestin2 to the MOR, but also efficaciously antagonized the effect of DAMGO in MOR-βarr2eGFP-U2OS cells in the β-arrestin2 recruitment assay. At the in vivo level, NAQ displayed a potent inhibition of the analgesic effect of morphine in the tail-flick assay (ID50=1.19 mg/kg). NAQ (10 mg/kg) also significantly decreased the hyper-locomotion induced by acute morphine without inducing any vertical jumps. Meanwhile NAQ precipitated lesser withdrawal symptoms in morphine dependent mice than naloxone. In conclusion, NAQ may represent a new chemical entity for opioid abuse and addiction treatment.

Indexed as

AnalgesicsAnimalsArrestinsBehavior, Animalbeta-ArrestinsCell Line, TumorEnkephalin, Ala(2)-MePhe(4)-Gly(5)-HumansIsoquinolinesLigandsMaleMice, Inbred ICRMorphinansMorphineMotor ActivityNaloxone17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6alpha-(isoquinoline-3'-carboxamido)morphinanAnalgesicsArrestinsbeta-ArrestinsEnkephalin, Ala(2)-MePhe(4)-Gly(5)-IsoquinolinesLigandsMorphinansMorphineNaloxoneNarcotic AntagonistsReceptors, Opioid, muAntagonistin vitroin vivoMu opioid receptorNAQPharmacology

Identifiers

PMID24815322
PMCPMC4073486
OpenAlexW2040400366

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Registered trials

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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.