The Emerging Importance of Transporter Proteins in the Psychopharmacological Treatment of the Pregnant Patient

Wang, Jun Sheng; Newport, D. Jeffrey; Stowe, Zachary N.; Donovan, Jennifer L.; Pennell, Page B.; DeVane, C. Lindsay

doi:10.1080/03602530701690390

Cited by 30 publications

(19 citation statements)

References 133 publications

(130 reference statements)

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“…, 2006). PDZK1 increases in vitro the transport activity of SLC22A11/OAT4 (cell surface expression increases) and SLC22A5/OCTN2 (cell surface expression does not increase), which are expressed in human placenta (Wang et al. , 2007).…”

Section: Drug Transporters In Human Placentamentioning

confidence: 99%

“…Currently, P‐gp is among the best studied transporters in human placenta (for reviews, see Ceckova‐Novotna et al. , 2006; Behravan and Piquette‐Miller, 2007; Wang et al. , 2007).…”

Section: Abcb1 and Abcb4 (P‐gps) In Placentamentioning

confidence: 99%

“…Many polymorphisms of ABCB1/MDR1/P‐gp have been characterized with clinical significance to drug resistance and pharmacokinetics of its substrates (Wang et al. , 2007; Zhou, 2008).…”

Section: Abcb1 and Abcb4 (P‐gps) In Placentamentioning

confidence: 99%

“…The SLC22 family (see Rizwan and Burckhardt, 2007) includes the OAT4 (SLC22A11/OAT4), which is the only transporter specific for humans and expressed mainly in placenta and kidney. There are discrepancies in the published values for the SLC gene number as well as the chromosomal localization of OAT4 [SLC22A11 at 11q13.1 (Rizwan and Burckhardt, 2007), SLC22A9 at 11q12.3 (Wang et al. (2007) or SLC22A11 (Ugele et al.…”

Section: Oats (Slc10 Slc21a3‐a15 Slc22a6‐a12)mentioning

confidence: 99%

“…Important paths for endogenous and exogenous compounds through biological membranes, including membranes in the blood-placental barrier, are provided by specialized transporter proteins (Klaassen and Lu, 2008). Transporters in several groups take part in drug transport: In the large group of ATP-binding cassette (ABC) transporters with 52 members, five proteins are heavily involved in drug transport: ABCB1/ P-glycoprotein (P-gp)/MDR1, ABCC1-3/MRP1-3 and ABCG2/ breast cancer resistance protein (BCRP) (see Leslie et al, 2005;Sarkadi et al, 2006;Behravan and Piquette-Miller, 2007;Wang et al, 2007;Zhou, 2008). In addition, ATP-independent transporters in solute carrier protein (SLC) families as well as monoamine, monocarboxylate and nucleoside transporters also transport drugs (Unadkat et al, 2004;Koepsell et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Drug transporters in the human blood‐placental barrier

Vähäkangas

Myllynen

2009

British J Pharmacology

249

184

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Studies on the increasing number of transporters found in the placental barrier are gaining momentum, because of their tissue‐specific expression, significance in physiology and disease, and the possible utilization of the emerging knowledge in pharmacology. In the placenta, both syncytiotrophoblast and fetal capillary endothelium express transporters. Fetal exposure is determined by the net effect of combination of transporters, their nature and localization in relation to placental cells and their substrate specificity. Although the significance of placental transporters on human fetal drug exposure is almost an unstudied field so far, their potential use to design drugs that do not cross the placenta is already being pursued. It is thus of interest to review the existing knowledge of human placental transporters. Transporters in all groups which take part in drug transport are found in human placenta. Especially, ATP‐binding cassette transporters ABCG2/breast cancer resistance protein, ABCB1/P‐glycoprotein and ABCC2/MRP2 are all expressed at the apical surface of syncytiotrophoblast facing maternal blood and are putatively important protective proteins both for placental tissue and the fetus, because they are efflux transporters and their substrates include many drugs and also environmental chemicals. Such protective effect has been shown in animals, but these results cannot be directly extrapolated to humans due to interspecies differences in placental structure and function. Experimental models utilizing human placental tissue, especially human placental perfusion, offer valuable possibilities, which have been insufficiently studied so far.

show abstract

Section: Drug Transporters In Human Placentamentioning

confidence: 99%

“…Currently, P‐gp is among the best studied transporters in human placenta (for reviews, see Ceckova‐Novotna et al. , 2006; Behravan and Piquette‐Miller, 2007; Wang et al. , 2007).…”

Section: Abcb1 and Abcb4 (P‐gps) In Placentamentioning

confidence: 99%

“…Many polymorphisms of ABCB1/MDR1/P‐gp have been characterized with clinical significance to drug resistance and pharmacokinetics of its substrates (Wang et al. , 2007; Zhou, 2008).…”

Section: Abcb1 and Abcb4 (P‐gps) In Placentamentioning

confidence: 99%

Section: Oats (Slc10 Slc21a3‐a15 Slc22a6‐a12)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Drug transporters in the human blood‐placental barrier

Vähäkangas

Myllynen

2009

British J Pharmacology

249

184

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Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study

Arumugasaamy

Gudelsky

Hurley-Novatny

et al. 2019

Adv Healthcare Materials

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Medications taken during pregnancy may significantly impact fetal development, yet there are few studies that rigorously assess medication safety due to ethical concerns. Selective serotonin reuptake inhibitors (SSRIs) are a class of drug increasingly being prescribed for depression, yet multiple studies have shown that taking SSRIs during pregnancy can lead to preterm birth and potential health concerns for the baby. Therefore, a biomimetic placental barrier model is utilized herein to assess transport profiles and phenotypic effects resulting from SSRI exposure, comparing fluoxetine and sertraline. Results show that the placental barrier quickly uptakes drug from the maternal side, but slowly releases on the fetal side. Phenotypically, there is a dose‐dependent change in cell adhesion molecule (CAM) and transforming growth factor beta (TGFβ) secretions, markers of cell adhesion and angiogenesis. Both drugs impact CAM secretions, whereas sertraline alone impacts TGFβ secretions. When evaluating cell type, it becomes clear that endothelial cells, not trophoblast, are the main cell type involved in these phenotypic changes. Overall, these findings further the understanding of SSRI transplacental transport and drug‐induced effects on the placental barrier.

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Placental Transfer of Antidepressant Medications: Implications for Postnatal Adaptation Syndrome

et al. 2015

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Seven to thirteen percent of women are either prescribed or taking (depending on the study) an antidepressant during pregnancy [1]. Although generally low risk, antidepressants have been associated with postnatal adaptation syndrome [2]. Because antidepressants freely cross into the intrauterine environment, it is our aim to summarize the current findings on placental transfer of antidepressants. The antidepressants reviewed are limited to those that are commonly prescribed to the pregnant patient suffering from depression or anxiety. The biological mechanisms regulating placental transport are both complex and multi-determined. Placental anatomy and pharmacokinetics are reviewed along with the latest advances in the understanding of active cellular molecular transport and placental metabolism. In addition, we consider how non-placental and fetal factors contribute to the distribution of drugs across the placenta. The data on placental passage of antidepressants is discussed in the context of the three commonly used research methodologies: animal models, ex vivo perfusion models, and in vivo models. The goal of this review is to inform clinical decision-making by improving understanding of how placental and pharmacokinetic factors relate to the data on antidepressant drug transfer and postnatal adaptation syndrome (PNAS). Incorporating maternal and fetal genetics will be the next step in assisting clinicians to make more informed choices regarding which antidepressants are the least likely to have extensive fetal exposure.

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The Emerging Importance of Transporter Proteins in the Psychopharmacological Treatment of the Pregnant Patient

Cited by 30 publications

References 133 publications

Drug transporters in the human blood‐placental barrier

Drug transporters in the human blood‐placental barrier

Model Placental Barrier Phenotypic Response to Fluoxetine and Sertraline: A Comparative Study

Placental Transfer of Antidepressant Medications: Implications for Postnatal Adaptation Syndrome

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