Evidence map›Paper›PMID 41959165›Full record

ArticlebioRxiv : the preprint server for biology2026

Melanocortin receptor 4 agonist setmelanotide treats opioid-induced respiratory depression.

Mateus R Amorim, Noah R Williams, Melanie A Ruiz, Junia L de Deus, O Aung, Olga Dergacheva, Joan Escobar, Mi-Kyung Shin, Cole R Winston, Thales H C Furquim and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Mateus R AmorimDepartment of Physiology, Medical School of Ribeirao Preto, SP, Brazil.
Noah R WilliamsDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
Melanie A RuizDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
Junia L de DeusDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
O AungMedical College of Wisconsin, Milwaukee, WI.
Olga DergachevaDepartment of Pharmacology and Physiology, George Washington University, Washington, DC.
Joan EscobarDepartment of Pharmacology and Physiology, George Washington University, Washington, DC.
Mi-Kyung ShinDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
Cole R WinstonDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
Thales H C FurquimDepartment of Physiology, Medical School of Ribeirao Preto, SP, Brazil.
Jeffrey S BergerDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.
David MendelowitzDepartment of Pharmacology and Physiology, George Washington University, Washington, DC.
Vsevolod Y PolotskyDepartment of Anesthesiology and Critical Care Medicine, George Washington University, Washington, DC.

Funding

Melanocortin 4 signaling in the carotid body in obesityR01HL133100 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Vsevolod Y Polotsky, Wan-yee Tang · 2016 to 2026
$7.1M
Treatment of Sleep Apnea by Targeting Leptin SignalingR01HL128970 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MENDELOWITZ, DAVID, POLOTSKY, VSEVOLOD Y · 2015 to 2023
$5.4M
The role of the melanocortin 4 receptor in control of breathingR01HL174409 · NHLBI · GEORGE WASHINGTON UNIVERSITY · PI David Mendelowitz, Vsevolod Y Polotsky · 2024 to 2026
$2.5M
NHLBI NIH HHS R01 HL128970NHLBI NIH HHS R01 HL133100NHLBI NIH HHS R01 HL174409
6 · The paper itself

Abstract

Background: The primary cause of death associated with opioids is opioid-induced respiratory depression (OIRD). Naloxone is used to reverse OIRD, but this drug is a competitive antagonist of μ-opioid receptor (MOR) and reverses analgesia, which limits its therapeutic use. Alternative non-opioid receptor antagonist-based approaches to OIRD treatment and prevention are needed. The aim of this study was to evaluate if setmelanotide (SET) is capable of reversing OIRD in a mouse model. Methods: C57BL/6J male and female mice and Sprague-Dawley rats were given IP morphine or fentanyl and then treated 15 min later with either SET or vehicle VEH (IP) in a random order. Breathing was recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. Results: In mice with OIRD, SET induced a 3-fold reduction of the apnea index, and decreased apnea duration as compared to the VEH treatment. SET increased respiratory rate and did not affect opioid-induced analgesia. Photostimulation of MC4R+ ChR2-expressing fibers in the parafacial region of MC4R-Cre mice elicited short-latency excitatory postsynaptic current in rostral ventral respiratory group (rVRG) pre-motoneurons projecting to the phrenic nucleus in the C3-C4 ventral horns of the spinal cord. Fentanyl inhibited the activity of rVRG neurons and SET reversed this effect. Conclusions: SET effectively treated OIRD by increasing respiratory rate and inducing a significant decrease in the number of apneas without decreasing analgesia.

Indexed as

analgesiaMelanocortin receptor 4plethysmographyrespiratory controlsynaptic transmission

Identifiers

PMID41959165
PMCPMC13061029

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.