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Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study

This determination of the mitochondrial effect of pharmacologically different antidepressants (agomelatine, ketamine and vortioxetine) was evaluated and quantified in vitro in pig brain-isolated mitochondria. We measured the activity of mitochondrial complexes, citrate synthase, malate dehydrogenase...

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Autores principales: Ľupták, Matej, Fišar, Zdeněk, Hroudová, Jana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697131/
https://www.ncbi.nlm.nih.gov/pubmed/36430306
http://dx.doi.org/10.3390/ijms232213824
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author Ľupták, Matej
Fišar, Zdeněk
Hroudová, Jana
author_facet Ľupták, Matej
Fišar, Zdeněk
Hroudová, Jana
author_sort Ľupták, Matej
collection PubMed
description This determination of the mitochondrial effect of pharmacologically different antidepressants (agomelatine, ketamine and vortioxetine) was evaluated and quantified in vitro in pig brain-isolated mitochondria. We measured the activity of mitochondrial complexes, citrate synthase, malate dehydrogenase and monoamine oxidase, and the mitochondrial respiratory rate. Total hydrogen peroxide production and ATP production were assayed. The most potent inhibitor of all mitochondrial complexes and complex I-linked respiration was vortioxetine. Agomelatine and ketamine inhibited only complex IV activity. None of the drugs affected complex II-linked respiration, citrate synthase or malate dehydrogenase activity. Hydrogen peroxide production was mildly increased by agomelatine, which might contribute to increased oxidative damage and adverse effects at high drug concentrations. Vortioxetine significantly reduced hydrogen peroxide concentrations, which might suggest antioxidant mechanism activation. All tested antidepressants were partial MAO-A inhibitors, which might contribute to their antidepressant effect. We observed vortioxetine-induced MAO-B inhibition, which might be linked to decreased hydrogen peroxide formation and contribute to its procognitive and neuroprotective effects. Mitochondrial dysfunction could be linked to the adverse effects of vortioxetine, as vortioxetine is the most potent inhibitor of mitochondrial complexes and complex I-linked respiration. Clarifying the molecular interaction between drugs and mitochondria is important to fully understand their mechanism of action and the connection between their mechanisms and their therapeutic and/or adverse effects.
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spelling pubmed-96971312022-11-26 Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study Ľupták, Matej Fišar, Zdeněk Hroudová, Jana Int J Mol Sci Article This determination of the mitochondrial effect of pharmacologically different antidepressants (agomelatine, ketamine and vortioxetine) was evaluated and quantified in vitro in pig brain-isolated mitochondria. We measured the activity of mitochondrial complexes, citrate synthase, malate dehydrogenase and monoamine oxidase, and the mitochondrial respiratory rate. Total hydrogen peroxide production and ATP production were assayed. The most potent inhibitor of all mitochondrial complexes and complex I-linked respiration was vortioxetine. Agomelatine and ketamine inhibited only complex IV activity. None of the drugs affected complex II-linked respiration, citrate synthase or malate dehydrogenase activity. Hydrogen peroxide production was mildly increased by agomelatine, which might contribute to increased oxidative damage and adverse effects at high drug concentrations. Vortioxetine significantly reduced hydrogen peroxide concentrations, which might suggest antioxidant mechanism activation. All tested antidepressants were partial MAO-A inhibitors, which might contribute to their antidepressant effect. We observed vortioxetine-induced MAO-B inhibition, which might be linked to decreased hydrogen peroxide formation and contribute to its procognitive and neuroprotective effects. Mitochondrial dysfunction could be linked to the adverse effects of vortioxetine, as vortioxetine is the most potent inhibitor of mitochondrial complexes and complex I-linked respiration. Clarifying the molecular interaction between drugs and mitochondria is important to fully understand their mechanism of action and the connection between their mechanisms and their therapeutic and/or adverse effects. MDPI 2022-11-10 /pmc/articles/PMC9697131/ /pubmed/36430306 http://dx.doi.org/10.3390/ijms232213824 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ľupták, Matej
Fišar, Zdeněk
Hroudová, Jana
Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study
title Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study
title_full Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study
title_fullStr Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study
title_full_unstemmed Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study
title_short Agomelatine, Ketamine and Vortioxetine Attenuate Energy Cell Metabolism—In Vitro Study
title_sort agomelatine, ketamine and vortioxetine attenuate energy cell metabolism—in vitro study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697131/
https://www.ncbi.nlm.nih.gov/pubmed/36430306
http://dx.doi.org/10.3390/ijms232213824
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AT fisarzdenek agomelatineketamineandvortioxetineattenuateenergycellmetabolisminvitrostudy
AT hroudovajana agomelatineketamineandvortioxetineattenuateenergycellmetabolisminvitrostudy