Multiple drug transporters mediate the placental transport of sulpiride.
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Bai M, Ma Z, Sun D, Zheng C, Weng Y, Yang X, Jiang T, Jiang H
Multiple drug transporters mediate the placental transport of sulpiride.
Arch Toxicol. 2017 Dec;91(12):3873-3884. doi: 10.1007/s00204-017-2008-8. Epub 2017 Jun 9.
- PubMed ID
- 28597291 [ View in PubMed]
- Abstract
Sulpiride is a typical antipsychotic drug for the treatment of schizophrenia, depression and other psychological disorders. It has been proven that a small amount of sulpiride could cross the human placenta using an ex vivo placental perfusion model. However, the placental transfer mechanism has not been elucidated. Considering the structure of sulpiride, we speculated that the transporters expressed in placenta might be involved in sulpiride uptake across the blood-placenta barrier. The aim of our study was to determine which transporters contributed to the placental transfer of sulpiride. Our results revealed that sulpiride was a substrate of human organic cation transporter (hOCT) 3, human multidrug resistance protein (hMDR) 1 and human breast cancer resistance protein (hBCRP) using transfected cells expressing respective transporters. In addition, the accumulation of sulpiride in BeWo cells (a human choriocarcinoma cell line) was obviously affected by inhibitors of carnitine/organic cation transporter (OCTN) 2, MDR1 and BCRP. The accumulation of sulpiride in primary human trophoblast cells was obviously affected by inhibitors of OCT3, OCTN1 and OCTN2. The above results indicate that hOCTN1 and hOCTN2 likely contribute to the sulpiride uptake from maternal circulation to trophoblast cells, while hMDR1 and hBCRP mediate the efflux from trophoblast cells to maternal circulation, and hOCT3 probably is involved in the bidirectional transport of sulpiride between the placenta and fetal blood.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Sulpiride ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Sulpiride P-glycoprotein 1 Protein Humans UnknownSubstrateDetails Sulpiride Solute carrier family 22 member 3 Protein Humans UnknownSubstrateDetails