Evidence map›Paper›PMID 33976311›Full record

ArticleScientific reports2021

D-Cystine di(m)ethyl ester reverses the deleterious effects of morphine on ventilation and arterial blood gas chemistry while promoting antinociception.

Benjamin Gaston, Santhosh M Baby, Walter J May, Alex P Young, Alan Grossfield, James N Bates, James M Seckler, Christopher G Wilson, Stephen J Lewis

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Reversal of morphine-induced respiratory depression with the µAmerican journal of physiology. Lung cellular and molecular physiology · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Erythrocytic metabolism of ATLX-0199: An agent that increases minute ventilation.Biochemical and biophysical research communications · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  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
  20. 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

9 authors at 7 institutions in 1 country.

Benjamin GastonHerman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Santhosh M BabyTranslational Sciences Treatment Discovery, Galvani Bioelectronics, Inc., 1250 S Collegeville Rd., Collegeville, PA, 1r9426, USA.
Walter J MayPediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Alex P YoungPediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Alan GrossfieldDepartment of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY, 14642, USA.
James N BatesDepartment of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA, 52242, USA.
James M SecklerDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
Christopher G WilsonBasic Sciences, Division of Physiology, School of Medicine, Loma Linda University, Loma Linda, CA, 92350, USA.
Stephen J LewisDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH, 44106, USA. sjl78@case.edu.
Case Western Reserve University · USUniversity of Virginia · USBioElectronics (United States) · USIndiana University School of MedicineLoma Linda University · USUniversity of Iowa Hospitals and Clinics · USUniversity of Rochester Medical Center · US

Funding

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
Sudaxine as an analgesia sparing respiratory stimulant for use in critical careR61HL154136 · NHLBI · INDIANA UNIVERSITY INDIANAPOLIS · PI GASTON, BENJAMIN, LEWIS, STEPHEN JOHN · 2020 to 2021
$1.1M
NHLBI NIH HHS R61 HL154136NIDA NIH HHS U01 DA051373
6 · The paper itself

Abstract

We have identified thiolesters that reverse the negative effects of opioids on breathing without compromising antinociception. Here we report the effects of D-cystine diethyl ester (D-cystine diEE) or D-cystine dimethyl ester (D-cystine diME) on morphine-induced changes in ventilation, arterial-blood gas chemistry, A-a gradient (index of gas-exchange in the lungs) and antinociception in freely moving rats. Injection of morphine (10 mg/kg, IV) elicited negative effects on breathing (e.g., depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive). Subsequent injection of D-cystine diEE (500 μmol/kg, IV) elicited an immediate and sustained reversal of these effects of morphine. Injection of morphine (10 mg/kg, IV) also elicited pronounced decreases in arterial blood pH, pO

Indexed as

Analgesics, OpioidAnimalsBlood Gas AnalysisCarbon DioxideCystineDrug Evaluation, PreclinicalHydrogen-Ion ConcentrationMaleMorphineOxygenPulmonary VentilationRatsRats, Sprague-DawleyAnalgesics, OpioidCarbon DioxideCystinecystine dimethyl esterMorphineOxygen

Identifiers

PMID33976311
PMCPMC8113454
OpenAlexW3163648648

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.