Evidence map›Paper›PMID 26428352›Full record

ArticleThe international journal of neuropsychopharmacology2015

Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study.

Chris A Oosterhof, Mostafa El Mansari, Christoffer Bundgaard, Pierre Blier

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 38% 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, 20 citations in OpenAlex.

  1. Review
  2. Mechanism of Action of Atypical Antipsychotic Drugs in Mood Disorders.International journal of molecular sciences · 2020
    Review
  3. Review
  4. Review
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

4 authors at 1 institution in 1 country.

Chris A OosterhofInstitute of Mental Health Research (Dr Oosterhof, Dr El Mansari, and Dr Blier), and Department of Cellular and Molecular Medicine (Dr Oosterhof and Dr Blier), University of Ottawa, Ottawa, Ontario, Canada; Neuroscience Drug Discovery, H. Lundbeck A/S, Valby, Denmark (Dr Bundgaard). Pierre.Blier@rohcg.on.ca.
Mostafa El MansariInstitute of Mental Health Research (Dr Oosterhof, Dr El Mansari, and Dr Blier), and Department of Cellular and Molecular Medicine (Dr Oosterhof and Dr Blier), University of Ottawa, Ottawa, Ontario, Canada; Neuroscience Drug Discovery, H. Lundbeck A/S, Valby, Denmark (Dr Bundgaard).
Christoffer BundgaardInstitute of Mental Health Research (Dr Oosterhof, Dr El Mansari, and Dr Blier), and Department of Cellular and Molecular Medicine (Dr Oosterhof and Dr Blier), University of Ottawa, Ottawa, Ontario, Canada; Neuroscience Drug Discovery, H. Lundbeck A/S, Valby, Denmark (Dr Bundgaard).
Pierre BlierInstitute of Mental Health Research (Dr Oosterhof, Dr El Mansari, and Dr Blier), and Department of Cellular and Molecular Medicine (Dr Oosterhof and Dr Blier), University of Ottawa, Ottawa, Ontario, Canada; Neuroscience Drug Discovery, H. Lundbeck A/S, Valby, Denmark (Dr Bundgaard).
University of Ottawa · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBrexpiprazole was recently approved as adjunctive therapy for depression and treatment of schizophrenia in adults. To complement results from a previous study in which its acute effects were characterized, the present study assessed the effect of repeated brexpiprazole administration on monoaminergic systems.

methodsBrexpiprazole (1mg/kg, subcutaneous) or vehicle was administered once daily for 2 and 14 days. Single-unit electrophysiological recordings from noradrenaline neurons in the locus coeruleus, serotonin neurons in the dorsal raphe nucleus, dopaminergic neurons in the ventral tegmental area, and pyramidal neurons in the hippocampus CA3 region were obtained in adult male Sprague-Dawley rats under chloral hydrate anesthesia within 4 hours after final dosing.

resultsBrexpiprazole blunted D2 autoreceptor responsiveness, while firing activity of ventral tegmental area dopaminergic neurons remained unaltered. Brexpiprazole increased the firing rate of locus coeruleus noradrenaline neurons and increased noradrenaline tone on α2-adrenergic receptors in the hippocampus. Administration of brexpiprazole for 2 but not 14 days increased the firing rate of serotonin neurons in the dorsal raphe nucleus. In the hippocampus, serotonin1A receptor blockade significantly disinhibited pyramidal neurons after 2- and 14-day brexpiprazole administration. In contrast, no significant disinhibition occurred after 24-hour washout or acute brexpiprazole.

conclusionsRepeated brexpiprazole administration resulted in a marked occupancy of D2 autoreceptors, while discharge activity of ventral tegmental area dopaminergic neurons remained unaltered. Brexpiprazole enhanced serotonergic and noradrenergic tone in the hippocampus, effects common to antidepressant agents. Together, these results provide further insight in the neural mechanisms by which brexpiprazole exerts antidepressant and antipsychotic effects.

Indexed as

Action PotentialsAnimalsBody WeightBrainDopamineMaleNeuronsNeurotransmitter AgentsNorepinephrinePsychotropic DrugsQuinolonesRats, Sprague-DawleyReceptors, NeurotransmitterSerotoninThiophenesTime FactorsbrexpiprazoleDopamineNeurotransmitter AgentsNorepinephrinePsychotropic DrugsQuinolonesReceptors, NeurotransmitterSerotoninThiophenesbrexpiprazoledopaminenorepinephrineserotoninsingle unit electrophysiological recordings

Identifiers

PMID26428352
PMCPMC4815476
OpenAlexW2180613923

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.