Evidence map›Paper›PMID 33585961›Full record

ArticlePsychopharmacology2021

Synergistic antihyperalgesic and antinociceptive effects of morphine and methyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate (MP-III-024): a positive allosteric modulator at α2GABA

Mohammad A Rahman, Thomas M Keck, Michael M Poe, Dishary Sharmin, James M Cook, Bradford D Fischer

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

Article in Psychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. 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 at 3 institutions in 1 country.

Mohammad A RahmanDepartment of Chemistry & Biochemistry, Department of Molecular & Cellular Biosciences, Rowan University, Glassboro, NJ, 08028, USA.
Thomas M KeckDepartment of Chemistry & Biochemistry, Department of Molecular & Cellular Biosciences, Rowan University, Glassboro, NJ, 08028, USA.
Michael M PoeDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA.
Dishary SharminDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA.
James M CookDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA.
Bradford D FischerDepartment of Biomedical Sciences Camden, Cooper Medical School of Rowan University, Camden, NJ, 08103, USA. fischerb@rowan.edu.
University of Wisconsin–Milwaukee · USRowan University · USCooper Medical School of Rowan University · US

Funding

Tolerance and Physical Dependence after Chronic Benzodiazepine TreatmentR01DA043204 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI JAMES K ROWLETT · 2017 to 2026
$4.3M
Synthesis of Alpha2/Alpha3 GABA Agonists to Treat Neuropathic PainR01NS076517 · NINDS · UNIVERSITY OF WISCONSIN MILWAUKEE · PI COOK, JAMES M · 2012 to 2015
$1.3M
Abuse liability and anti-addiction potential of the atypical mu opioid receptor agonist IBNtxAR03DA041560 · NIDA · ROWAN UNIVERSITY · PI KECK, THOMAS MCGOWAN · 2017 to 2017
$109k
NIDA NIH HHS DA043204NIDA NIH HHS R01 DA043204NIDA NIH HHS R03 DA041560NINDS NIH HHS NS076517NINDS NIH HHS R01 NS076517
6 · The paper itself

Abstract

rationaleOpioid and GABA

objectiveThe purpose of this study was to examine the interactive effects of the μ-opioid agonist morphine and the α2GABA

methodsThe antihyperalgesic and antinociceptive effects of morphine and MP-III-024 administered alone were assessed initially, followed by fixed-ratio mixtures of MP-III-024/morphine combinations. Drug interaction data were analyzed using isobolographic and dose-addition analyses. All studies were conducted in male CD-1 mice.

resultsIn the assay of mechanical hyperalgesia, each compound produced dose-dependent antihyperalgesic effects, whereas only morphine was effective on thermal nociception. Fixed-ratio mixtures of MP-III-024/morphine were also dose-dependently effective in both procedures. These drug combination studies revealed that morphine and MP-III-024 produced supra-additive (synergistic) effects in both assays, depending on their relative proportions.

conclusionsThese results demonstrate an interaction between α2GABA

Indexed as

Analgesics, OpioidAnimalsDose-Response Relationship, DrugDrug InteractionsDrug SynergismHyperalgesiaMaleMiceMorphinePainReceptors, GABA-AReceptors, Opioid, muAnalgesics, OpioidMorphineReceptors, GABA-AReceptors, Opioid, muAnalgesiaBenzodiazepinesDose-additionGABA receptorsIsobolographic analysisOpioids

Identifiers

PMID33585961
PMCPMC8141038
OpenAlexW3129299578

What OpenQuestion holds

Textmetadata
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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.