Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
05
01
2023
accepted:
13
06
2023
revised:
14
05
2023
medline:
2
11
2023
pubmed:
30
6
2023
entrez:
29
6
2023
Statut:
ppublish
Résumé
Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.
Identifiants
pubmed: 37386057
doi: 10.1038/s41380-023-02134-8
pii: 10.1038/s41380-023-02134-8
pmc: PMC10618096
doi:
Substances chimiques
Trimetazidine
N9A0A0R9S8
Vasodilator Agents
0
Antioxidants
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3231-3242Subventions
Organisme : Stanley Medical Research Institute (SMRI)
ID : 21T-005
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 1156072
Organisme : Department of Health | National Health and Medical Research Council (NHMRC)
ID : 2017131
Informations de copyright
© 2023. The Author(s).
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