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Sertraline Alters Multidrug Resistance Phosphoglycoprotein Activity in the Mouse Placenta and Fetal Blood–Brain Barrier

Abstract

Phosphoglycoprotein (P-gp) is highly expressed in the placental syncytiotrophoblast and prevents xenobiotics from entering the fetus. In tumor cells, P-gp-mediated substrate efflux is inhibited by selective serotonin reuptake inhibitors (SSRIs). However, nothing is known regarding the effects of SSRIs on P-gp function in the placenta or fetal tissues. We hypothesized that the SSRI sertraline would decrease P-gp-mediated drug efflux at the placenta and fetal blood–brain barrier (BBB)—increasing P-gp substrate transfer from the mother to the fetus and fetal brain. In contrast to our hypothesis, this study presents the novel findings that sertraline (4 hours exposure) increases placental P-gp-mediated efflux (P < .001), resulting in decreased drug transfer to the fetus. Meanwhile, sertraline decreases fetal (P < .001) and maternal (P < .05) BBB P-gp-mediated efflux, resulting in increased drug transfer into the fetal and maternal brain from the circulation. This suggests that P-gp regulation by sertraline is tissue specific. These findings have important clinical implications with respect to fetal protection during maternal drug therapy in pregnancy.

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Correspondence to Stephen G. Matthews PhD.

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Bhuiyan, M., Petropoulos, S., Gibb, W. et al. Sertraline Alters Multidrug Resistance Phosphoglycoprotein Activity in the Mouse Placenta and Fetal Blood–Brain Barrier. Reprod. Sci. 19, 407–415 (2012) doi:10.1177/1933719111424438

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Keywords

  • placenta
  • brain
  • multidrug resistance phosphoglycoprotein
  • sertraline
  • [3H]digoxin