Evidence map›Paper›PMID 31535696›Full record

ArticleAlcohol and alcoholism (Oxford, Oxfordshire)2019

Probenecid Reduces Alcohol Drinking in Rodents. Is Pannexin1 a Novel Therapeutic Target for Alcohol Use Disorder?

Brendan J Tunstall, Irene Lorrai, Sam A McConnell, Katrina L Gazo, Lia J Zallar, Giordano de Guglielmo, Ivy Hoang, Carolina L Haass-Koffler, Vez Repunte-Canonigo, George F Koob and 2 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alcohol and alcoholism (Oxford, Oxfordshire), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04218357 (Probenecid as Pharmacotherapy for Alcohol Use Disorder), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 26% 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.

NCT04218357 phase1completednot on this mapstarted 2020, after this paper: background citation

Probenecid as Pharmacotherapy for Alcohol Use Disorder

TypeinterventionalSponsorBrown UniversityRan2020 to 2023Enrolled35ConditionsAlcohol Use DisorderArmsProbenecid or placebo single administration
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 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 4 institutions in 2 countries.

Brendan J TunstallNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Irene LorraiDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Sam A McConnellNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Katrina L GazoNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Lia J ZallarNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Giordano de GuglielmoDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Ivy HoangDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Carolina L Haass-KofflerCenter for Alcohol and Addiction Studies; Department of Psychiatry and Human Behavior; Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA.
Vez Repunte-CanonigoDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
George F KoobNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Leandro F VendruscoloNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Pietro Paolo SannaDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
National Institutes of Health · USScripps Research Institute · USBrown University · USUniversity of California San Diego · US

Funding

Gene Network Perturbations in Alcohol Dependence - A Systems BiologyApproachR01AA021667 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI Vez REPUNTE-CANONIGO, PIETRO P SANNA · 2013 to 2026
$6.1M
Systems biology of HIV, methamphetamine and antiretrovirals interactionsR01DA041750 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI KARAN, CHARLES, RISSMAN, ROBERT · 2016 to 2020
$4.4M
Identification of small molecules for neurological complications of HIV and substance abuse comorbidityR01DA046204 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI SANNA, PIETRO P, SPICER, TIMOTHY PATRICK · 2018 to 2022
$4.2M
Systems biology of RNA Modifications in HIV/AIDS and Substance Use DisordersR01DA046170 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI SANNA, PIETRO P · 2018 to 2022
$3.8M
Neural substrates of opiate-HIV interactions.R01DA043268 · NIDA · SCRIPPS RESEARCH INSTITUTE, THE · PI SANNA, PIETRO P · 2016 to 2020
$2.9M
Epigenetic regulation of alcohol tolerance and dependence by methyl CpG binding protein 2R01AA025012 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI SANNA, PIETRO P · 2017 to 2021
$1.8M
NIAAA NIH HHS R01 AA021667NIAAA NIH HHS R01 AA025012NIDA NIH HHS R01 DA041750NIDA NIH HHS R01 DA043268NIDA NIH HHS R01 DA046170NIDA NIH HHS R01 DA046204
6 · The paper itself

Abstract

aimsThe development of novel and more effective medications for alcohol use disorder (AUD) is an important unmet medical need. Drug repositioning or repurposing is an appealing strategy to bring new therapies to the clinic because it greatly reduces the overall costs of drug development and expedites the availability of treatments to those who need them. Probenecid, p-(di-n-propylsulfamyl)-benzoic acid, is a drug used clinically to treat hyperuricemia and gout due to its activity as an inhibitor of the kidneys' organic anion transporter that reclaims uric acid from urine. Probenecid also inhibits pannexin1 channels that are involved in purinergic neurotransmission and inflammation, which have been implicated in alcohol's effects and motivation for alcohol. Therefore, we tested the effects of probenecid on alcohol intake in rodents.

methodsWe tested the effects of probenecid on operant oral alcohol self-administration in alcohol-dependent rats during acute withdrawal as well as in nondependent rats and in the drinking-in-the-dark (DID) paradigm of binge-like drinking in mice.

resultsProbenecid reduced alcohol intake in both dependent and nondependent rats and in the DID paradigm in mice without affecting water or saccharin intake, indicating that probenecid's effect was selective for alcohol and not the result of a general reduction in reward.

conclusionsThese results raise the possibility that pannexin1 is a novel therapeutic target for the treatment of AUD. The clinical use of probenecid has been found to be generally safe, suggesting that it can be a candidate for drug repositioning for the treatment of AUD.

Indexed as

Adjuvants, PharmaceuticAlcohol DrinkingAlcoholismAnimalsConnexinsDose-Response Relationship, DrugDrug Delivery SystemsEthanolMaleMiceMice, Inbred C57BLNerve Tissue ProteinsProbenecidRatsRats, WistarSelf AdministrationAdjuvants, PharmaceuticConnexinsEthanolNerve Tissue ProteinsPanx1 protein, mouseProbenecid

Identifiers

PMID31535696
PMCPMC6751410
OpenAlexW2973841237

What OpenQuestion holds

Textmetadata
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Registered trials

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.