Evidence map›Paper›PMID 26791602›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

The Selective Monoacylglycerol Lipase Inhibitor MJN110 Produces Opioid-Sparing Effects in a Mouse Neuropathic Pain Model.

Jenny L Wilkerson, Micah J Niphakis, Travis W Grim, Mohammed A Mustafa, Rehab A Abdullah, Justin L Poklis, William L Dewey, Hamid Akbarali, Matthew L Banks, Laura E Wise and 2 more

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

Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
7.3field-weighted citation impact, top 3% 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

43 citing papers in PubMed, 67 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

12 authors at 2 institutions in 1 country.

Jenny L WilkersonDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.) jenny.wilkerson@vcuhealth.org.
Micah J NiphakisDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Travis W GrimDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Mohammed A MustafaDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Rehab A AbdullahDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Justin L PoklisDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
William L DeweyDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Hamid AkbaraliDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Matthew L BanksDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Laura E WiseDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Benjamin F CravattDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Aron H LichtmanDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (J.L.W., T.W.G., M.A.M., R.A.A., J.L.P., W.L.D., H.A., M.L.B., L.E.W., A.H.L.); and The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California (M.J.N., B.F.C.).
Virginia Commonwealth University · USScripps Research Institute · US

Funding

VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI Matthew Sean Halquist · 2014 to 2026
$13.8M
SYNTHESIS OF SR141716A AND ANANDAMIDE ANALOGSP01DA009789 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI MECHOULAM, RAPHAEL · 1995 to 2013
$11.6M
STRUCTURAL STUDIES OF FAAHP01DA017259 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI STEVENS, RAYMOND C · 2004 to 2013
$10.6M
Monoacylglycerol Lipase Inhibitors for Treating Opioid Use Disorders (RO)R01DA032933 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F, LICHTMAN, ARON H · 2012 to 2014
$1.5M
Inhibiting peripheral diacylglycerol lipase beta - a novel target for pain reliefF32DA038493 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI WILKERSON, JENNY · 2015 to 2017
$157k
NIDA NIH HHS F32-DA033934-01A1NIDA NIH HHS F32 DA038493NIDA NIH HHS P01 DA009789NIDA NIH HHS P01-DA009789NIDA NIH HHS P01 DA017259NIDA NIH HHS P01-DA017259NIDA NIH HHS P30 DA033934NIDA NIH HHS R01 DA032933NIDA NIH HHS R01-DA032933
6 · The paper itself

Abstract

Serious clinical liabilities associated with the prescription of opiates for pain control include constipation, respiratory depression, pruritus, tolerance, abuse, and addiction. A recognized strategy to circumvent these side effects is to combine opioids with other antinociceptive agents. The combination of opiates with the primary active constituent of cannabis (Δ(9)-tetrahydrocannabinol) produces enhanced antinociceptive actions, suggesting that cannabinoid receptor agonists can be opioid sparing. Here, we tested whether elevating the endogenous cannabinoid 2-arachidonoylglycerol through the inhibition of its primary hydrolytic enzyme monoacylglycerol lipase (MAGL), will produce opioid-sparing effects in the mouse chronic constriction injury (CCI) of the sciatic nerve model of neuropathic pain. The dose-response relationships of i.p. administration of morphine and the selective MAGL inhibitor 2,5-dioxopyrrolidin-1-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate (MJN110) were tested alone and in combination at equieffective doses for reversal of CCI-induced mechanical allodynia and thermal hyperalgesia. The respective ED50 doses (95% confidence interval) of morphine and MJN110 were 2.4 (1.9-3.0) mg/kg and 0.43 (0.23-0.79) mg/kg. Isobolographic analysis of these drugs in combination revealed synergistic antiallodynic effects. Acute antinociceptive effects of the combination of morphine and MJN110 required μ-opioid, CB1, and CB2 receptors. This combination did not reduce gastric motility or produce subjective cannabimimetic effects in the drug discrimination assay. Importantly, combinations of MJN110 and morphine given repeatedly (i.e., twice a day for 6 days) continued to produce antiallodynic effects with no evidence of tolerance. Taken together, these findings suggest that MAGL inhibition produces opiate-sparing events with diminished tolerance, constipation, and cannabimimetic side effects.

Indexed as

Analgesics, OpioidAnimalsArachidonic AcidsBehavior, AnimalCarbamatesConstriction, PathologicDisease Models, AnimalDose-Response Relationship, DrugDrug SynergismEndocannabinoidsEnzyme InhibitorsGlyceridesHyperalgesiaMaleMiceMice, Inbred C57BLAnalgesics, OpioidArachidonic AcidsCarbamatesEndocannabinoidsEnzyme InhibitorsGlyceridesglyceryl 2-arachidonateMJN110Monoacylglycerol LipasesMorphineReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Receptors, Opioid, muSuccinimides

Identifiers

PMID26791602
PMCPMC4809319
OpenAlexW2301252870

What OpenQuestion holds

Textmetadata
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.