Evidence map›Paper›PMID 27307500›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2016

Discriminative Stimulus Properties of the Endocannabinoid Catabolic Enzyme Inhibitor SA-57 in Mice.

Robert A Owens, Bogna Ignatowska-Jankowska, Mohammed Mustafa, Patrick M Beardsley, Jenny L Wiley, Abdulmajeed Jali, Dana E Selley, Micah J Niphakis, Benjamin F Cravatt, Aron H Lichtman

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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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.9field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Cannabinoid CBThe Journal of pharmacology and experimental therapeutics · 2017
    Article
  3. Article
  4. 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

10 authors at 2 institutions in 1 country.

Robert A OwensDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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.).
Bogna Ignatowska-JankowskaDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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 MustafaDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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.).
Patrick M BeardsleyDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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 L WileyDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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.).
Abdulmajeed JaliDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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.).
Dana E SelleyDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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.).
Micah J NiphakisDepartment of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia (R.A.O., B.I.J., M.M., P.M.B., A.J., D.E.S., A.H.L.); RTI International, Research Triangle Park, North Carolina (J.L.W.); 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.) alichtma@vcu.edu.
RTI International · USVirginia Commonwealth University Medical Center · US

Funding

TRAINING IN THE PHARMACOLOGY OF ABUSED DRUGST32DA007027 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI William L. Dewey · 1985 to 2026
$14.7M
VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI YAN ZHANG · 2014 to 2026
$13.8M
Virginia Commonwealth University Initiative for Maximizing Student DevelopmentR25GM090084 · NIGMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI AKBARALI, HAMID I, LLOYD, JOYCE A. · 2010 to 2022
$5.2M
Endocannabinoid modulation of pain-depressed behaviorR01DA030404 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI NEGUS, SIDNEY S, SIM-SELLEY, LAURA J · 2011 to 2020
$3.7M
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
Endocannabinoid DiscriminationR01DA026449 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI WILEY, JENNY L. · 2010 to 2014
$1.5M
NIDA NIH HHS P30 DA033934NIDA NIH HHS R01 DA026449NIDA NIH HHS R01 DA030404NIDA NIH HHS R01 DA032933NIDA NIH HHS T32 DA007027NIGMS NIH HHS R25 GM090084
6 · The paper itself

Abstract

Whereas the inhibition of fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL), the respective major hydrolytic enzymes of N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), elicits no or partial substitution for Δ(9)-tetrahydrocannabinol (THC) in drug-discrimination procedures, combined inhibition of both enzymes fully substitutes for THC, as well as produces a constellation of cannabimimetic effects. The present study tested whether C57BL/6J mice would learn to discriminate the dual FAAH-MAGL inhibitor SA-57 (4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester) from vehicle in the drug-discrimination paradigm. In initial experiments, 10 mg/kg SA-57 fully substituted for CP55,940 ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol), a high-efficacy CB1 receptor agonist in C57BL/6J mice and for AEA in FAAH (-/-) mice. Most (i.e., 23 of 24) subjects achieved criteria for discriminating SA-57 (10 mg/kg) from vehicle within 40 sessions, with full generalization occurring 1 to 2 hours postinjection. CP55,940, the dual FAAH-MAGL inhibitor JZL195 (4-​nitrophenyl 4-​(3-​phenoxybenzyl)piperazine-​1-​carboxylate), and the MAGL inhibitors MJN110 (2,5-dioxopyrrolidin-1-yl 4-(bis(4-chlorophenyl)methyl)piperazine-1-carboxylate) and JZL184 (4-[Bis(1,3-benzodioxol-5-yl)hydroxymethyl]-1-piperidinecarboxylic acid 4-nitrophenyl ester) fully substituted for SA-57. Although the FAAH inhibitors PF-3845 ((N-3-pyridinyl-4-[[3-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenyl]methyl]-1-piperidinecarboxamide) and URB597 (cyclohexylcarbamic acid 3'-(aminocarbonyl)-[1,1'-biphenyl]-3-yl ester) did not substitute for SA-57, PF-3845 produced a 2-fold leftward shift in the MJN110 substitution dose-response curve. In addition, the CB1 receptor antagonist rimonabant blocked the generalization of SA-57, as well as substitution of CP55,940, JZL195, MJN110, and JZL184. These findings suggest that MAGL inhibition plays a major role in the CB1 receptor-mediated SA-57 training dose, which is further augmented by FAAH inhibition.

Indexed as

AcetamidesAmidohydrolasesAnimalsCarbamatesCyclohexanolsDiscrimination, PsychologicalDose-Response Relationship, DrugEndocannabinoidsEnzyme InhibitorsFatty Acid Amide HydrolasesMaleMiceMice, Inbred C57BLMonoacylglycerol Lipases3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol4-(2-(4-chlorophenyl)ethyl)-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl esterAcetamidesAmidohydrolasesCarbamatesCyclohexanolsEndocannabinoidsEnzyme InhibitorsFatty Acid Amide HydrolasesMonoacylglycerol Lipases

Identifiers

PMID27307500
PMCPMC4959103
OpenAlexW2439945613

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.