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Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives

Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb seroton...

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Autores principales: Horackova, Hana, Karahoda, Rona, Cerveny, Lukas, Vachalova, Veronika, Ebner, Ronja, Abad, Cilia, Staud, Frantisek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397948/
https://www.ncbi.nlm.nih.gov/pubmed/34452265
http://dx.doi.org/10.3390/pharmaceutics13081306
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author Horackova, Hana
Karahoda, Rona
Cerveny, Lukas
Vachalova, Veronika
Ebner, Ronja
Abad, Cilia
Staud, Frantisek
author_facet Horackova, Hana
Karahoda, Rona
Cerveny, Lukas
Vachalova, Veronika
Ebner, Ronja
Abad, Cilia
Staud, Frantisek
author_sort Horackova, Hana
collection PubMed
description Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term placenta perfusion) and ex vivo (uptake studies in membrane vesicles isolated from healthy human term placenta). All tested antidepressants significantly inhibited SERT- and OCT3-mediated serotonin uptake in a dose-dependent manner. Calculated half-maximal inhibitory concentrations (IC(50)) were in the range of therapeutic plasma concentrations. Using in vitro and in situ models, we further showed that the placental efflux transporters did not compromise mother-to-fetus transport of antidepressants. Collectively, we suggest that antidepressants have the potential to affect serotonin levels in the placenta or fetus when administered at therapeutic doses. Interestingly, the effect of antidepressants on serotonin homeostasis in rat placenta was sex dependent. As accurate fetal programming requires optimal serotonin levels in the fetoplacental unit throughout gestation, inhibition of SERT-/OCT3-mediated serotonin uptake may help explain the poor outcomes of antidepressant use in pregnancy.
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spelling pubmed-83979482021-08-29 Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives Horackova, Hana Karahoda, Rona Cerveny, Lukas Vachalova, Veronika Ebner, Ronja Abad, Cilia Staud, Frantisek Pharmaceutics Article Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term placenta perfusion) and ex vivo (uptake studies in membrane vesicles isolated from healthy human term placenta). All tested antidepressants significantly inhibited SERT- and OCT3-mediated serotonin uptake in a dose-dependent manner. Calculated half-maximal inhibitory concentrations (IC(50)) were in the range of therapeutic plasma concentrations. Using in vitro and in situ models, we further showed that the placental efflux transporters did not compromise mother-to-fetus transport of antidepressants. Collectively, we suggest that antidepressants have the potential to affect serotonin levels in the placenta or fetus when administered at therapeutic doses. Interestingly, the effect of antidepressants on serotonin homeostasis in rat placenta was sex dependent. As accurate fetal programming requires optimal serotonin levels in the fetoplacental unit throughout gestation, inhibition of SERT-/OCT3-mediated serotonin uptake may help explain the poor outcomes of antidepressant use in pregnancy. MDPI 2021-08-20 /pmc/articles/PMC8397948/ /pubmed/34452265 http://dx.doi.org/10.3390/pharmaceutics13081306 Text en © 2021 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
Horackova, Hana
Karahoda, Rona
Cerveny, Lukas
Vachalova, Veronika
Ebner, Ronja
Abad, Cilia
Staud, Frantisek
Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives
title Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives
title_full Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives
title_fullStr Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives
title_full_unstemmed Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives
title_short Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives
title_sort effect of selected antidepressants on placental homeostasis of serotonin: maternal and fetal perspectives
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397948/
https://www.ncbi.nlm.nih.gov/pubmed/34452265
http://dx.doi.org/10.3390/pharmaceutics13081306
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