Evidence map›Paper›PMID 41174091›Full record

ArticlePsychopharmacology2026

Effects of TPA023B, an α2/3/5GABA

Loc M Pham, Andria B Nanney, Jordan Hasting, Daniela Rüedi-Bettschen, Kevin B Freeman, James K Rowlett

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 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

6 authors.

Loc M PhamDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA.
Andria B NanneyDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA.
Jordan HastingDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA.
Daniela Rüedi-BettschenDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA.
Kevin B FreemanDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA.
James K RowlettDepartment of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA. jrowlett@umc.edu.ORCID http://orcid.org/0000-0002-4077-5017

Funding

ANXIOLYTIC EFFECTS AND ABUSE OF BZ RECEPTOR LIGANDSR01DA011792 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI ROWLETT, JAMES K · 1998 to 2024
$7.8M
Deterrents for prescription opioid abuseR01DA039167 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI FREEMAN, KEVIN B. · 2015 to 2025
$4.9M
Tolerance and Physical Dependence after Chronic Benzodiazepine TreatmentR01DA043204 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI JAMES K ROWLETT · 2017 to 2026
$4.3M
Fentanyl use during pregnancy: impact on dam, placenta, and offspring development.R01DA059181 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI Daniela Rüedi-Bettschen · 2023 to 2026
$2.0M
Investigation of in vivo efficacy of G-protein biased mu opioid receptor agonists.F31DA056209 · NIDA · UNIVERSITY OF MISSISSIPPI MED CTR · PI PHAM, LOC M · 2022 to 2024
$120k
NIDA NIH HHS DA0039167NIDA NIH HHS DA011792NIDA NIH HHS DA043204NIDA NIH HHS DA056209NIDA NIH HHS DA059181NIDA NIH HHS F31 DA056209NIDA NIH HHS R01 DA011792NIDA NIH HHS R01 DA039167NIDA NIH HHS R01 DA043204NIDA NIH HHS R01 DA059181
6 · The paper itself

Abstract

rationaleOpioid-related overdose deaths involving benzodiazepines have increased in recent years, and prior studies have reported that clinically used benzodiazepines can enhance the respiratory-depressant effects of mu opioid receptor (MOR) agonists. TPA023B is an α1-sparing GABA

objectivesThe current study compared the effects of either TPA023B or midazolam, alone and combined with fentanyl, on respiratory depression in rats, using whole-body plethysmography.

methodsMale Sprague-Dawley rats were implanted with chronic indwelling intravenous (i.v.) catheters for drug infusions. Respiration (frequency, tidal volume, and minute volume) was measured using whole-body plethysmography. The tests consisted of a pretreatment (midazolam, 30 mg/kg; i.v.; TPA023B, 1.0 mg/kg; i.v; or vehicle) followed by a fentanyl injection (0.01, 0.03, 0.1 mg/kg, i.v., or vehicle) and 60 min of respiration assessment.

resultsOverall, fentanyl alone, but not TPA023B or midazolam alone, produced dose-dependent reductions in tidal volume and minute volume. When administered as pre-treatments, neither midazolam nor TPA023B increased the magnitude of fentanyl-induced respiratory depression, instead producing prolonged reductions in tidal volume and minute volume. Midazolam produced a more sustained reduction in these parameters than TPA023B.

conclusionsBenzodiazepines prolong fentanyl-induced respiratory depression, but this effect may be reduced by eliminating activity at α1GABA

Indexed as

FentanylMidazolamRespiratory InsufficiencyAllosteric RegulationAnalgesics, OpioidAnimalsDose-Response Relationship, DrugMalePlethysmography, Whole BodyPyridazinesRatsRats, Sprague-DawleyReceptors, GABA-ATriazoles7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo(4,3-b)pyridazineAnalgesics, OpioidFentanylMidazolamPyridazinesReceptors, GABA-ATriazolesFentanylMidazolamRespiratory depressionTPA023BWhole-body plethysmography

Identifiers

PMID41174091
PMCPMC13370654

What OpenQuestion holds

Textmetadata
LicenceTDM
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.