Evidence map›Paper›PMID 37922109›Full record

ArticleNeurotoxicity research2023

Metergoline Shares Properties with Atypical Antipsychotic Drugs Identified by Gene Expression Signature Screen.

Chiara C Bortolasci, Emily J Jaehne, Damián Hernández, Briana Spolding, Timothy Connor, Bruna Panizzutti, Olivia M Dean, Tamsyn M Crowley, Alison R Yung, Laura Gray and 4 more

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

Article in Neurotoxicity research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 48% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. 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

14 authors at 2 institutions in 2 countries.

Chiara C BortolasciThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Emily J JaehneSchool of Psychology and Public Health, La Trobe University, Bundoora, Australia.
Damián HernándezThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia. d.hernandez@deakin.edu.au.
Briana SpoldingThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Timothy ConnorThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Bruna PanizzuttiThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Olivia M DeanThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Tamsyn M CrowleyThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Alison R YungThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Laura GrayThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Jee Hyun KimThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Maarten van den BuuseSchool of Psychology and Public Health, La Trobe University, Bundoora, Australia.
Michael BerkThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Ken WalderThe Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia.
Deakin University · AULa Trobe University · AU

Funding

National Health and Medical Research Council 1136829National Health and Medical Research Council 1156072
6 · The paper itself

Abstract

Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed. Biological pathways with an increased gene expression included circadian rhythm and vascular endothelial growth factor signalling, while the adherens junction and cell cycle pathways were transcriptionally downregulated. The Connectivity Map (CMap) analysis screen highlighted drugs that affect global gene expression in a similar manner to these psychiatric disorder treatments, including several other antipsychotic drugs, confirming the utility of this approach. The CMap screen specifically identified metergoline, an ergot alkaloid currently used to treat seasonal affective disorder, as a drug of interest. In mice, metergoline dose-dependently reduced MK-801- or methamphetamine-induced locomotor hyperactivity confirming the potential of metergoline to treat positive symptoms of schizophrenia in an animal model. Metergoline had no effects on prepulse inhibition deficits induced by MK-801 or methamphetamine. Taken together, metergoline appears a promising drug for further studies to be repurposed as a treatment for schizophrenia and possibly other psychiatric disorders.

Indexed as

Antipsychotic AgentsMajor Depressive DisorderMethamphetamineAnimalsDizocilpine MaleateHumansMetergolineMiceTranscriptomeVascular Endothelial Growth Factor AAntipsychotic AgentsDizocilpine MaleateMetergolineMethamphetamineVascular Endothelial Growth Factor ADrug discoveryNeurosciencePsychiatric disordersPsychiatryPsychosisTreatment

Identifiers

PMID37922109
PMCPMC10682262
OpenAlexW4388298249

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.