Evidence map›Paper›PMID 34248639›Full record

ArticleFrontiers in pharmacology2021

Systemic Administration of Tempol Attenuates the Cardiorespiratory Depressant Effects of Fentanyl.

Santhosh Baby, Ryan Gruber, Joseph Discala, Veljko Puskovic, Nijo Jose, Feixiong Cheng, Michael Jenkins, James Seckler, Stephen Lewis

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 24 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

9 authors at 3 institutions in 2 countries.

Santhosh BabyGalleon Pharmaceuticals, Inc., Horsham, PA, United States.
Ryan GruberGalleon Pharmaceuticals, Inc., Horsham, PA, United States.
Joseph DiscalaGalleon Pharmaceuticals, Inc., Horsham, PA, United States.
Veljko PuskovicGalleon Pharmaceuticals, Inc., Horsham, PA, United States.
Nijo JoseDepartment of Radiotherapy and Oncology, Kasturba Medical College, Manipal, India.
Feixiong ChengGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States.
Michael JenkinsDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
James SecklerDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
Stephen LewisDepartment of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
Case Western Reserve University · USCleveland Clinic Lerner College of Medicine · USKasturba Medical College, Manipal · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fentanyl is a high-potency opioid receptor agonist that elicits profound analgesia and suppression of breathing in humans and animals. To date, there is limited evidence as to whether changes in oxidant stress are important factors in any of the actions of acutely administered fentanyl. This study determined whether the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), or a potent antioxidant, N-acetyl-L-cysteine methyl ester (L-NACme), modify the cardiorespiratory and analgesic actions of fentanyl. We examined whether the prior systemic injection of Tempol or L-NACme affects the cardiorespiratory and/or analgesic responses elicited by the subsequent injection of fentanyl in isoflurane-anesthetized and/or freely moving male Sprague-Dawley rats. Bolus injections of Tempol (25, 50 or 100 mg/kg, IV) elicited minor increases in frequency of breathing, tidal volume and minute ventilation. The ventilatory-depressant effects of fentanyl (5 μg/kg, IV) given 15 min later were dose-dependently inhibited by prior injections of Tempol. Tempol elicited dose-dependent and transient hypotension that had (except for the highest dose) resolved when fentanyl was injected. The hypotensive responses elicited by fentanyl were markedly blunted after Tempol pretreatment. The analgesic actions of fentanyl (25 μg/kg, IV) were not affected by Tempol (100 mg/kg, IV). L-NACme did not modify any of the effects of fentanyl. We conclude that prior administration of Tempol attenuates the cardiorespiratory actions of fentanyl without affecting the analgesic effects of this potent opioid. As such, Tempol may not directly affect opioid-receptors that elicit the effects of fentanyl. Whether, the effects of Tempol are solely due to alterations in oxidative stress is in doubt since the powerful antioxidant, L-NACme, did not affect fentanyl-induced suppression of breathing.

Indexed as

cardiorespiratory depressionfentanylsprague-dawley ratssuperoxide dismutasetempol

Identifiers

PMID34248639
PMCPMC8260831
OpenAlexW3174206706

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.