Evidence map›Paper›PMID 30001114›Full record

ArticleACS chemical neuroscience2018

Methylation Products of 6β- N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators.

Yi Zheng, Samuel Obeng, Huiqun Wang, David L Stevens, Essie Komla, Dana E Selley, William L Dewey, Hamid I Akbarali, Yan Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS chemical neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 6 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

9 authors at 1 institution in 1 country.

Yi ZhengDepartment of Medicinal Chemistry , Virginia Commonwealth University , 800 E. Leigh Street , Richmond , Virginia 23298 , United States.
Samuel ObengDepartment of Medicinal Chemistry , Virginia Commonwealth University , 800 E. Leigh Street , Richmond , Virginia 23298 , United States.
Huiqun WangDepartment of Medicinal Chemistry , Virginia Commonwealth University , 800 E. Leigh Street , Richmond , Virginia 23298 , United States.
David L StevensDepartment of Pharmacology and Toxicology , Virginia Commonwealth University , 1112 East Clay Street , Richmond , Virginia 23298 , United States.
Essie KomlaDepartment of Pharmacology and Toxicology , Virginia Commonwealth University , 1112 East Clay Street , Richmond , Virginia 23298 , United States.
Dana E SelleyDepartment of Pharmacology and Toxicology , Virginia Commonwealth University , 1112 East Clay Street , Richmond , Virginia 23298 , United States.
William L DeweyDepartment of Pharmacology and Toxicology , Virginia Commonwealth University , 1112 East Clay Street , Richmond , Virginia 23298 , United States.
Hamid I AkbaraliDepartment of Pharmacology and Toxicology , Virginia Commonwealth University , 1112 East Clay Street , Richmond , Virginia 23298 , United States.
Yan ZhangDepartment of Medicinal Chemistry , Virginia Commonwealth University , 800 E. Leigh Street , Richmond , Virginia 23298 , United States.ORCID 0000-0001-8934-7016
Virginia Commonwealth University · US

Funding

Non-peptide Mu Opioid Receptor Selective AntagonistsR01DA024022 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2009 to 2019
$3.5M
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
NIDA NIH HHS R01 DA024022NIDA NIH HHS R01 DA044855
6 · The paper itself

Abstract

Two 6β- N-heterocyclic naltrexamine derivatives, NAP and NMP, have been identified as peripherally selective mu opioid receptor (MOR) antagonists. To further enhance the peripheral selectivity of both compounds, the 17-amino group and the nitrogen atom of the pyridine ring in both NAP and NMP were methylated to obtain dMNAP and dMNMP, respectively. Compared with NAP and NMP, the binding affinities of dMNAP and dMNMP shifted to MOR and KOR (kappa opioid receptor) dual selective and they acted as moderate efficacy partial agonists. The results from radioligand binding studies were further confirmed by molecular docking studies. In vivo studies demonstrated that dMNAP and dMNMP did not produce antinociception nor did they antagonize morphine's antinociceptive activity, indicating that these compounds did not act on the central nervous system. Meanwhile, both dMNAP and dMNMP significantly slowed down fecal excretion, which indicated that they were peripherally acting opioid receptor agonists. All together, these results suggested that dMNAP and dMNMP acted as peripheral mu/kappa opioid receptor modulators and may be applicable in the treatment of diarrhea in patients with bowel dysfunction.

Indexed as

Analgesics, OpioidAnimalsCHO CellsConstipationCricetulusDiarrheaDrug Partial AgonismGastrointestinal AgentsGastrointestinal TransitImidazolesMethylationMiceMolecular Docking SimulationMorphineNaltrexoneNarcotic AntagonistsAnalgesics, OpioideluxadolineGastrointestinal AgentsImidazolesmethylnaltrexoneMorphineNaltrexoneNAP naltrexamineNarcotic AntagonistsPhenylalanineQuaternary Ammonium CompoundsReceptors, Opioid, deltaReceptors, Opioid, kappaReceptors, Opioid, mudiarrheairritable bowel syndromeMethylationnaltrexamineopioid bowel dysfunctionperipheral opioid receptor modulators

Identifiers

PMID30001114
PMCPMC6344324
OpenAlexW2821679023

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.