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Sertraline alters multidrug resistance phosphoglycoprotein activity in the mouse placenta and fetal blood-brain barrier.
MedLine Citation:
PMID:  22510699     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Manzerul Bhuiyan; Sophie Petropoulos; William Gibb; Stephen G Matthews
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Reproductive sciences (Thousand Oaks, Calif.)     Volume:  19     ISSN:  1933-7205     ISO Abbreviation:  Reprod Sci     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101291249     Medline TA:  Reprod Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  407-15     Citation Subset:  IM    
Affiliation:
1Department of Physiology, University of Toronto, Toronto , Canada.
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