Evidence map›Paper›PMID 39064909›Full record

ArticleMolecules (Basel, Switzerland)2024

Effects of Selective and Mixed-Action Kappa and Delta Opioid Receptor Agonists on Pain-Related Behavioral Depression in Mice.

S Stevens Negus, Celsey M St Onge, Young K Lee, Mengchu Li, Kenner C Rice, Yan Zhang

Abstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2024. 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
–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. Article
  2. Article
  3. Review
  4. Article
  5. Review
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

6 authors.

S Stevens NegusDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0001-8471-645X
Celsey M St OngeDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-9845-7118
Young K LeeDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Mengchu LiDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Kenner C RiceDrug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 9800 Medical Center Drive, Bethesda, MD 20892, USA.ORCID 0000-0002-1147-9147
Yan ZhangDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0001-8934-7016

Funding

Medicinal Chemistry of Drugs Acting on Central and Peripheral Opioid ReceptorsZIADA000527 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI RICE, KENNER · 2009 to 2025
$23.2M
STEREOSELECTIVE ASPECTS OF BARBITURATE ABUSE POTENTIALR01DA003393 · NIDA · UNIVERSITY OF ARKANSAS MED SCIS LTL ROCK · PI WENGER, GALEN R · 1985 to 1985
–
National Institute on Drug Abuse (NIDA); National Institute on Neurological Disorders and Stroke (NINDS) P30DA033934; R61NS133217; UH3DA050311; UG3DA054785
6 · The paper itself

Abstract

We recently developed a series of nalfurafine analogs (TK10, TK33, and TK35) that may serve as non-addictive candidate analgesics. These compounds are mixed-action agonists at the kappa and delta opioid receptors (KOR and DOR, respectively) and produce antinociception in a mouse warm-water tail-immersion test while failing to produce typical mu opioid receptor (MOR)-mediated side effects. The warm-water tail-immersion test is an assay of pain-stimulated behavior vulnerable to false-positive analgesic-like effects by drugs that produce motor impairment. Accordingly, this study evaluated TK10, TK33, and TK35 in a recently validated assay of pain-related behavioral depression in mice that are less vulnerable to false-positive effects. For comparison, we also evaluated the effects of the MOR agonist/analgesic hydrocodone (positive control), the neurokinin 1 receptor (NK1R) antagonist aprepitant (negative control), nalfurafine as a selective KOR agonist, SNC80 as a selective DOR agonist, and a nalfurafine/SNC80 mixture. Intraperitoneal injection of dilute lactic acid (IP lactic acid) served as a noxious stimulus to depress vertical and horizontal locomotor activity in male and female ICR mice. IP lactic acid-induced locomotor depression was alleviated by hydrocodone but not by aprepitant, nalfurafine, SNC80, the nalfurafine/SNC80 mixture, or the KOR/DOR agonists. These results suggest that caution is warranted in advancing mixed-action KOR/DOR agonists as candidate analgesics.

Indexed as

PainReceptors, Opioid, deltaReceptors, Opioid, kappaAnalgesics, OpioidAnimalsBehavior, AnimalDepressionMaleMiceMorphinansSpiro CompoundsAnalgesics, OpioidMorphinansReceptors, Opioid, deltaReceptors, Opioid, kappaSpiro CompoundsTRK 820aprepitantdelta opioid receptorhydrocodonekappa opioid receptornalfurafinepain-depressed behaviorSNC80

Identifiers

PMID39064909
PMCPMC11279860

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.