Evidence map›Paper›PMID 35043597›Full record

ArticleChemMedChem2022

6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects.

Nicholas S Akins, Nisha Mishra, Hannah M Harris, Narendar Dudhipala, Seong Jong Kim, Adam W Keasling, Soumyajit Majumdar, Jordan K Zjawiony, Jason J Paris, Nicole M Ashpole and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. 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.

Nicholas S AkinsDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
Nisha MishraDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
Hannah M HarrisResearch Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Narendar DudhipalaDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Seong Jong KimNatural Products Utilization Research Unit, United States Department of Agriculture, Agricultural Research Service, University, MS 38677, USA.
Adam W KeaslingDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
Soumyajit MajumdarResearch Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA.
Jordan K ZjawionyDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
Jason J ParisDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
Nicole M AshpoleDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
Hoang V LeDepartment of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.ORCID 0000-0002-8392-7113

Funding

Pilot Project ProgramP30GM122733 · NIGMS · UNIVERSITY OF MISSISSIPPI · PI MAJUMDAR, SOUMYAJIT · 2018 to 2022
$5.3M
NIGMS NIH HHS P30 GM122733
6 · The paper itself

Abstract

Current common analgesics are mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. However, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold via an ester linker. In vitro studies showed that many of these compounds have dual agonism on kappa and mu opioid receptors. In vivo studies on the lead dual kappa and mu opioid receptor agonist demonstrated supraspinal thermal analgesic activity while avoiding anxiogenic effects in male mice, thus providing further strong evidence in support of the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

Indexed as

Receptors, Opioid, kappaReceptors, Opioid, muAnalgesicsAnalgesics, OpioidAnimalsDiterpenes, ClerodaneEstersMaleMiceAnalgesicsAnalgesics, OpioidDiterpenes, ClerodaneEstersReceptors, Opioid, kappaReceptors, Opioid, musalvinorin A

Identifiers

PMID35043597
PMCPMC9015904

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.