Evidence map›Paper›PMID 38010591›Full record

ArticleDrugs in R&D2024

Drug-Drug Interaction Studies of Esmethadone (REL-1017) Involving CYP3A4- and CYP2D6-Mediated Metabolism.

Nicola Ferri, Sara De Martin, James Stuart, Sergio Traversa, Franco Folli, Marco Pappagallo, Cedric O'Gorman, Clotilde Guidetti, Andrea Mattarei, Charles E Inturrisi and 1 more

Open access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Drugs in R&D, 2024. 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
0.7field-weighted citation impact, top 27% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

11 authors at 3 institutions in 1 country.

Nicola FerriDepartment of Medicine-DIMED, University of Padua, 35122, Padua, Italy. nicola.ferri@unipd.it.ORCID http://orcid.org/0000-0001-8898-7441
Sara De MartinDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122, Padua, Italy.
James StuartRelmada Therapeutics, Coral Gables, FL, 33134, USA.
Sergio TraversaRelmada Therapeutics, Coral Gables, FL, 33134, USA.
Franco FolliDepartment of Health Sciences, University of Milan, 20122, Milan, Italy.
Marco PappagalloRelmada Therapeutics, Coral Gables, FL, 33134, USA.
Cedric O'GormanRelmada Therapeutics, Coral Gables, FL, 33134, USA.
Clotilde GuidettiChild and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Pediatric Hospital, IRCCS, Rome, Italy.
Andrea MattareiDepartment of Pharmaceutical and Pharmacological Sciences, University of Padua, 35122, Padua, Italy.
Charles E InturrisiRelmada Therapeutics, Coral Gables, FL, 33134, USA.
Paolo L ManfrediRelmada Therapeutics, Coral Gables, FL, 33134, USA.
University of Padua · ITBambino Gesù Children's Hospital · ITUniversity of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveEsmethadone (dextromethadone; d-methadone; S-methadone (+)-methadone; REL-1017) is the opioid inactive dextro-isomer of racemic methadone. Esmethadone is a low potency N-methyl-D-aspartate (NMDA) receptor channel blocker with higher affinity for GluN2D subtypes. Esmethadone showed robust, rapid, and sustained antidepressant effects in patients with major depressive disorder (MDD) with inadequate response to ongoing serotonergic antidepressant treatment.

methodsHere we described the results of in vitro and phase 1 clinical trials aimed at investigating the esmethadone metabolism and possible drug-drug interactions.

resultsEsmethadone is primarily metabolized to EDDP (2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine) by multiple enzymes, including CYP3A4/5 and CYP2B6. In vitro studies showed that esmethadone inhibits CYP2D6 with IC

conclusionsIn summary, esmethadone demonstrated a negligible effect on CYP3A4 induction and its metabolism was not meaningfully affected by strong CYP3A4 inhibitors while it increased exposure of CYP2D6-metabolized drugs.

Indexed as

Analgesics, OpioidCytochrome P-450 CYP2D6Cytochrome P-450 CYP3AMethadonePyrrolidinesAdultCytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 CYP3A InhibitorsDrug InteractionsFemaleHumansMajor Depressive DisorderMaleMidazolamMiddle Aged2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidineAnalgesics, OpioidCYP3A4 protein, humanCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsMethadoneMidazolamPyrrolidines

Identifiers

PMID38010591
PMCPMC11035515
OpenAlexW4389045688

What OpenQuestion 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 OpenQuestion graph.