Evidence map›Paper›PMID 31473161›Full record

ArticleEuropean journal of pharmacology2019

D-578, an orally active triple monoamine reuptake inhibitor, displays antidepressant and anti-PTSD like effects in rats.

Aloke K Dutta, Soumava Santra, Arman Harutyunyan, Banibrata Das, Michael J Lisieski, Liping Xu, Tamara Antonio, Maarten E A Reith, Shane A Perrine

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 40% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Aloke K DuttaWayne State University, Department of Pharmaceutical Sciences, Detroit, MI, 48202, USA. Electronic address: adutta@wayne.edu.
Soumava SantraWayne State University, Department of Pharmaceutical Sciences, Detroit, MI, 48202, USA.
Arman HarutyunyanDepartment of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, USA.
Banibrata DasWayne State University, Department of Pharmaceutical Sciences, Detroit, MI, 48202, USA.
Michael J LisieskiDepartment of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, USA.
Liping XuWayne State University, Department of Pharmaceutical Sciences, Detroit, MI, 48202, USA.
Tamara AntonioNew York University, Department of Psychiatry, New York, NY, 10016, USA.
Maarten E A ReithNew York University, Department of Psychiatry, New York, NY, 10016, USA.
Shane A PerrineDepartment of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, USA.
Wayne State University · USNew York University · US

Funding

Novel Triple Uptake Inhibitors for Treatment of DepressionR01MH084888 · NIMH · WAYNE STATE UNIVERSITY · PI DUTTA, ALOKE K · 2009 to 2013
$1.9M
NIMH NIH HHS R01 MH084888RRD VA I01 RX002252
6 · The paper itself

Abstract

Significant unmet needs exist for development of better pharmacotherapeutic agents for major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) as the current drugs are inadequate. Our goal in this study is to investigate behavioral pharmacological characterization of a novel triple reuptake inhibitor (TRI) D-578 which exhibits nanomolar potency at all three monoamine transporters (Ki; 16.2. 16.2, 3.23 nM, and 29.6, 20.6, 6.10 nM for the rat brain and cloned human dopamine, serotonin and norepinephrine transporters, respectively) and exhibited little to no affinity for other off-target CNS receptors. In a rat forced swim test, compound D-578 upon oral administration displayed high efficacy and not stimulating in locomotor behavior. The effects of D-578 and paroxetine were next evaluated in a rat model for traumatic stress exposure - the single prolonged stress (SPS) model - which has been shown to have construct, predictive, and behavioral validity in modeling aspects of PTSD. Our results show that SPS had no effect on the acquisition of conditioned fear, but impaired extinction learning and extinction retention of fear behavior compared to sham treatment. D-578, but not paroxetine, attenuated the extinction and extinction-retention deficit induced by SPS. These findings suggest that D-578 has greater efficacy in normalizing traumatic stress-induced extinction-retention learning in a model for PTSD compared to paroxetine. Overall these results suggest that D-578, in addition to producing a robust and efficacious antidepressant effect, may attenuate maladaptive retention of fearful memories and support further testing of this agent for the pharmacotherapy of depression and PTSD.

Indexed as

Administration, OralAnimalsAntidepressive AgentsBehavior, AnimalBehavior Observation TechniquesDisease Models, AnimalDopamine Plasma Membrane Transport ProteinsDrug Evaluation, PreclinicalHumansMajor Depressive DisorderMaleNeurotransmitter Uptake InhibitorsNorepinephrine Plasma Membrane Transport ProteinsRatsRetention, PsychologySerotonin Plasma Membrane Transport ProteinsAntidepressive AgentsDopamine Plasma Membrane Transport ProteinsNeurotransmitter Uptake InhibitorsNorepinephrine Plasma Membrane Transport ProteinsSerotonin Plasma Membrane Transport ProteinsMajor depressive disorderPharmacotherapyPost-traumatic stress disorderSelective serotonin reuptake inhibitorTriple reuptake inhibitors

Identifiers

PMID31473161
PMCPMC9722229
OpenAlexW2971259668

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.