Logo image
Back
Metergoline Shares Properties with Atypical Antipsychotic Drugs Identified by Gene Expression Signature Screen
Journal article   Open access   Peer reviewed

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

Chiara C. Bortolasci, Emily J. Jaehne, Damian Hernandez, Briana Spolding, Timothy Connor, Bruna Panizzutti, Olivia M. Dean, Tamsyn M. Crowley, Alison R. Yung, Laura Gray, …
Neurotoxicity research, Vol.41(6), pp.502-513
12/2023
DOI: https://doi.org/10.1007/s12640-023-00673-0
PMID: 37922109
pdf
Metergoline Shares Properties with Atypical Antipsychotic Drugs932.93 kBDownloadView
Published (Version of record)CC BY V4.0,  Open Access
url
Metergoline Shares Properties with Atypical Antipsychotic DrugsView
Published (Version of record)CC BY V4.0,  Open

Related links

Metrics

3 Record Views
2 Times Cited - Web of Science

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

Source: InCites

Abstract

Psychiatric disorders Psychosis Treatment Psychiatry Neuroscience Drug discovery
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.

Details

Logo image