Evidence map›Paper›PMID 30640180›Full record

ArticleBehavioural pharmacology2019

Effects of the α2/α3-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 on pain-depressed behavior in rats: comparison with ketorolac and diazepam.

Megan J Moerke, Guanguan Li, Lalit K Golani, James Cook, S Stevens Negus

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

Article in Behavioural pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Antinociceptive Effects ofThe Journal of pharmacology and experimental therapeutics · 2024
    Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. GABAFrontiers in psychiatry · 2022
    Review
  7. Article
  8. Article
  9. The Positive Allosteric Modulator ofThe Journal of pharmacology and experimental therapeutics · 2020
    Article
  10. The α2,3-selective potentiator of GABAPharmacology, biochemistry, and behavior · 2019
    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

5 authors at 2 institutions in 1 country.

Megan J MoerkeDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia.
Guanguan LiDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Lalit K GolaniDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
James CookDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
S Stevens NegusDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia.
University of Wisconsin–Milwaukee · USVirginia Commonwealth University · US

Funding

TRAINING IN THE PHARMACOLOGY OF ABUSED DRUGST32DA007027 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI William L. Dewey · 1985 to 2026
$14.7M
Neurobiology and Treatment of PainR01NS070715 · NINDS · VIRGINIA COMMONWEALTH UNIVERSITY · PI NEGUS, SIDNEY S, SELLEY, DANA E · 2009 to 2018
$3.3M
Development of new drugs for asthma by targeting GABA(A) receptors in the lungR01HL118561 · NHLBI · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2014 to 2017
$2.0M
Design of New Therapeutic Agents to Treat SchizophreniaR01MH096463 · NIMH · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2013 to 2017
$1.9M
Synthesis of Alpha2/Alpha3 GABA Agonists to Treat Neuropathic PainR01NS076517 · NINDS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2012 to 2015
$1.3M
NHLBI NIH HHS R01 HL118561NIDA NIH HHS T32 DA007027NIMH NIH HHS R01 MH096463NINDS NIH HHS R01 NS070715NINDS NIH HHS R01 NS076517
6 · The paper itself

Abstract

This study examined effects of the α2/α3-subtype-selective GABAA receptor positive allosteric modulator KRM-II-81 in an assay of pain-related behavioral depression. Adult, male Sprague-Dawley rats responded for electrical brain stimulation in a frequency-rate intracranial self-stimulation (ICSS) procedure. Intraperitoneal injection of 1.8% lactic acid served as an acute noxious stimulus to depress ICSS. Effects of KRM-II-81 were evaluated in the absence and presence of the acid noxious stimulus. The NSAID ketorolac and the benzodiazepine diazepam were tested as comparators. Neither ketorolac nor KRM-II-81 altered ICSS in the absence of the acid noxious stimulus; however, diazepam produced facilitation consistent with its abuse liability. Ketorolac blocked acid-induced depression of ICSS, and effects of 1.0 mg/kg ketorolac lasted for at least 5 h. KRM-II-81 (1.0 mg/kg) produced significant antinociception after 30 min that dissipated by 60 min. Diazepam also attenuated acid-depressed ICSS, but only at doses that facilitated ICSS when administered alone. The lack of ketorolac or KRM-II-81 effects on ICSS in the absence of the acid noxious stimulus suggests low abuse liability for both compounds. The effectiveness of ketorolac to block acid-induced ICSS depression agrees with clinical analgesic efficacy of ketorolac. KRM-II-81 produced significant but less consistent and shorter-acting antinociception than ketorolac.

Indexed as

AnalgesicsAnimalsBehavior, AnimalConditioning, OperantDiazepamElectric StimulationKetorolacMaleOxazolesPainRatsRats, Sprague-DawleyReceptors, GABA-ASelf StimulationAnalgesicsDiazepamKetorolacKRM-II-81OxazolesReceptors, GABA-A

Identifiers

PMID30640180
PMCPMC6610697
OpenAlexW2912477090

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.