Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives.
Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives.
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选定的抗抑郁药对胎盘血清素稳态的影响：母亲和胎儿的观点。
DOI：
10.3390/pharmaceutics13081306
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发表时间：
2021-08-20
期刊：
影响因子：
5.4
通讯作者：
Staud F
中科院分区：
文献类型：
--
作者：
Horackova H;Karahoda R;Cerveny L;Vachalova V;Ebner R;Abad C;Staud F
抑郁症是一种普遍存在的疾病，影响多达20%的孕妇。因此，超过10%的人被处方抗抑郁药物，主要是5-羟色胺再摄取抑制剂（SSRI）和选择性5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRI）。我们假设抗抑郁药通过抑制5-羟色胺转运体（SERT）和有机阳离子转运体3（OCT 3）分别在母体和胎儿胎盘膜中干扰胎儿胎盘单位中的5-羟色胺稳态。帕罗西汀、西酞普兰、氟西汀、氟伏沙明、舍曲林和文拉法辛进行了原位（大鼠足月胎盘灌注）和离体（从健康人足月胎盘分离的膜囊泡中的摄取研究）测试。所有测试的抗抑郁药均以剂量依赖性方式显著抑制SERT和OCT 3介导的5-羟色胺摄取。计算的半数最大抑制浓度（IC 50）在治疗血浆浓度范围内。使用体外和原位模型，我们进一步表明，胎盘外排转运蛋白并不影响抗抑郁药的母婴转运。总的来说，我们认为抗抑郁药在治疗剂量下有可能影响胎盘或胎儿中的5-羟色胺水平。有趣的是，抗抑郁药对大鼠胎盘中5-羟色胺稳态的影响具有性别依赖性。由于准确的胎儿编程需要在整个妊娠期间胎儿胎盘单位中的最佳5-羟色胺水平，抑制SERT-/OCT 3介导的5-羟色胺摄取可能有助于解释妊娠期使用抗抑郁药的不良结局。
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 (IC50) 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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影响因子：
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