Evidence map›Paper›PMID 40777490›Full record

ArticlebioRxiv : the preprint server for biology2025

Membrane Permeability Drives the Extreme Potency of Fentanyl but not Isotonitazene.

Joseph Clayton, George J Farmer, Jacqueline Glenn, Shailesh N Mistry, J Robert Lane, Lei Shi, Lidiya Stavitskaya, Meritxell Canals, Jana Shen

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

9 authors.

Joseph ClaytonDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, U.S.A.ORCID 0000-0002-2652-5994
George J FarmerDivision of Biomolecular Science and Medicinal Chemistry, School of Pharmacy, and University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2UH, U.K.
Jacqueline GlennCentre of Membrane Proteins and Receptors, Universities of Nottingham and Birmingham, Midlands NG7 2UH, U.K.
Shailesh N MistryDivision of Biomolecular Science and Medicinal Chemistry, School of Pharmacy, and University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2UH, U.K.
J Robert LaneCentre of Membrane Proteins and Receptors, Universities of Nottingham and Birmingham, Midlands NG7 2UH, U.K.ORCID 0000-0002-7361-7875
Lei ShiComputational Chemistry and Molecular Biophysics Section, National Institutes on Drug Abuse - Intramural Research Program, Baltimore, MD 21224, U.S.A.ORCID 0000-0002-4137-096X
Lidiya StavitskayaDivision of Applied Regulatory Science, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, U.S.A.ORCID 0000-0002-6307-2314
Meritxell CanalsCentre of Membrane Proteins and Receptors, Universities of Nottingham and Birmingham, Midlands NG7 2UH, U.K.ORCID 0000-0002-7942-5006
Jana ShenDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, U.S.A.ORCID 0000-0002-3234-0769

Funding

Molecular mechanisms of proton-coupled dynamic processes in biologyR35GM148261 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI Jana Shen · 2023 to 2026
$1.5M
NIGMS NIH HHS R35 GM148261
6 · The paper itself

Abstract

Fentanyl is a leading cause of drug overdose deaths in the United States, yet the mechanisms underlying its extreme in vivo potency remain poorly understood. Recently, new synthetic opioids nitazene derivatives have emerged, among which isotonitazene is 50 times more potent than fentanyl. Here we used state-of-the-art molecular dynamics (MD) simulations and experiments to investigate the membrane-dependent pharmacology of fentanyl, isotonitazene, morphine, and naloxone. Using the weighted-ensemble continuous constant pH MD, we estimated the effective permeability of fentanyl at pH 7.5 to be on the order of 10

Identifiers

PMID40777490
PMCPMC12330492

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.