Evidence map›Paper›PMID 35814208›Full record

ArticleFrontiers in pharmacology2022

D-Cysteine Ethyl Ester Reverses the Deleterious Effects of Morphine on Breathing and Arterial Blood-Gas Chemistry in Freely-Moving Rats.

Paulina M Getsy, Santhosh M Baby, Walter J May, Alex P Young, Benjamin Gaston, Matthew R Hodges, Hubert V Forster, James N Bates, Christopher G Wilson, Tristan H J Lewis and 2 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 21 citations in OpenAlex.

  1. Dose- and time-dependent physiological effects of fentanyl in adult goats.Journal of applied physiology (Bethesda, Md. : 1985) · 2026
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  4. Review
  5. Reversal of morphine-induced respiratory depression with the µAmerican journal of physiology. Lung cellular and molecular physiology · 2025
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  18. L-NAC reverses of the adverse effects of fentanyl infusion on ventilation and blood-gas chemistry.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022
    Article
  19. 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

12 authors at 6 institutions in 1 country.

Paulina M GetsyDepartment of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
Santhosh M BabyDepartment of Drug Discovery, Galleon Pharmaceuticals, Inc., Horsham, PA, United States.
Walter J MayPediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Alex P YoungPediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States.
Benjamin GastonHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
Matthew R HodgesDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States.
Hubert V ForsterDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States.
James N BatesDepartment of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA, United States.
Christopher G WilsonBasic Sciences, Division of Physiology, School of Medicine, Loma Linda University, Loma Linda, CA, United States.
Tristan H J LewisDepartment of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
Yee-Hee HsiehDivision of Pulmonary, Critical Care and Sleep Medicine, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH, United States.
Stephen J LewisDepartment of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
Case Western Reserve University · USMedical College of Wisconsin · USUniversity of Virginia · USIndiana University School of MedicineLoma Linda University · USUniversity of Iowa Hospitals and Clinics · US

Funding

S-nitrosothiol signaling in pulmonary epithelial cellsP01HL101871 · NHLBI · UNIVERSITY OF VIRGINIA · PI GASTON, BENJAMIN, LEWIS, STEPHEN JOHN · 2011 to 2015
$8.7M
Optimization of novel thioesters as a therapeutic strategy for combating opioid overdoses and abuseU01DA051373 · NIDA · CASE WESTERN RESERVE UNIVERSITY · PI LEWIS, STEPHEN JOHN · 2020 to 2022
$1.5M
NHLBI NIH HHS P01 HL101871NIDA NIH HHS U01 DA051373
6 · The paper itself

Abstract

Cell-penetrant thiol esters including the disulfides, D-cystine diethyl ester and D-cystine dimethyl ester, and the monosulfide, L-glutathione ethyl ester, prevent and/or reverse the deleterious effects of opioids, such as morphine and fentanyl, on breathing and gas exchange within the lungs of unanesthetized/unrestrained rats without diminishing the antinociceptive or sedative effects of opioids. We describe here the effects of the monosulfide thiol ester, D-cysteine ethyl ester (D-CYSee), on intravenous morphine-induced changes in ventilatory parameters, arterial blood-gas chemistry, alveolar-arterial (A-a) gradient (i.e., index of gas exchange in the lungs), and sedation and antinociception in freely-moving rats. The bolus injection of morphine (10 mg/kg, IV) elicited deleterious effects on breathing, including depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive. Subsequent injections of D-CYSee (2 × 500 μmol/kg, IV, given 15 min apart) elicited an immediate and sustained reversal of these effects of morphine. Morphine (10 mg/kg, IV) also A-a gradient, which caused a mismatch in ventilation perfusion within the lungs, and elicited pronounced changes in arterial blood-gas chemistry, including pronounced decreases in arterial blood pH, pO

Indexed as

antinociceptionD-cysteine ethyl estergas exchangemorphinerespiratory depressionsedationSprague Dawley ratsthiol esters

Identifiers

PMID35814208
PMCPMC9260251
OpenAlexW4283323128

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.