Evidence map›Paper›PMID 42199972›Full record

ArticleCureus2026

Combination of the BK-Channel Antagonist ENA-001 and Naloxone Is More Effective Than Either Agent Alone in Reversing Fentanyl-Induced Respiratory Suppression in Rats.

Monichan Phay, Lia Kwee, Robert B Raffa, Thomas L Miller, Albert Dahan, Joseph V Pergolizzi

Abstract read
In one paragraph

Article in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Targeting the Carotid Body Function With Big-KPharmacology research & perspectives · 2026
    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

6 authors.

Monichan PhayNeuroscience, Ealden Lab, Philadelphia, USA.
Lia KweeNeuroscience, Ealden Lab, Philadelphia, USA.
Robert B RaffaPharmacy, Temple University, Philadelphia, USA.
Thomas L MillerClinical Development, Enalare Therapeutics Inc., Mullica Hill, USA.
Albert DahanResearch and Development, Enalare Therapeutics Inc., Mullica Hill, USA.
Joseph V PergolizziPain Management, NEMA Research, Naples, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Fentanyl overdose in humans produces two life-threatening effects: central μ-opioid receptor (MOR)-mediated hypoventilation and generalized muscle rigidity that further impairs ventilation. Naloxone, the current standard of care, reverses both effects via competitive antagonism at MOR; however, its clinical utility is limited, particularly in the setting of polydrug overdose, where nonopioid mechanism(s) may also contribute to respiratory suppression. ENA-001 restores ventilation as a peripherally directed (carotid body) BK-channel antagonist with a mechanism independent of MOR, and is "agnostic" to the drug cause of respiratory depression. The effectiveness of a combination has not yet been assessed. This study was designed to determine the nature of the pharmacodynamic interaction between naloxone and ENA-001 against fentanyl-induced effects related to overdose toxicity. Specifically, to determine whether their combined effect is neutral, additive, or antagonistic. Methods Fentanyl was administered to adult male Sprague Dawley rats as a single intravenous (i.v.) bolus injection via the lateral tail vein following pretreatment with naloxone and/or ENA-001 administered via intramuscular (i.m.) injection. A timer was started at the time of i.v. fentanyl injection, and hypoventilation and muscle rigidity were recorded to define the duration of early ventilatory suppression and the time to recovery from fentanyl-induced body rigidity. Results Pretreatment with naloxone and ENA-001 together was more effective (p < 0.001) in attenuating fentanyl-induced respiratory suppression than either agent alone (p < 0.05 and 0.01, respectively), and the combination did not compromise the body rigidity recovery timeline. Conclusions In this rat model of fentanyl-induced effects associated with overdose, coadministration of the combination of the opioid antagonist naloxone and the BK channel antagonist ENA-001 represents a potentially more effective treatment of fentanyl overdose than either agent alone.

Indexed as

bk channelcarotid bodyena-001fentanylmuscle rigiditynaloxoneratrespiratory depression

Identifiers

PMID42199972
PMCPMC13200216

What Socratic 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 Socratic graph.