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In-vitro and in situ assessment of the efflux of five antidepressants by breast cancer resistance protein
- Source :
- The Journal of pharmacy and pharmacology. 71(7)
- Publication Year :
- 2018
-
Abstract
- Objectives Antidepressants need to penetrate the blood–brain barrier (BBB) to exert their functions in the central nervous system. Breast cancer resistance protein (BCRP), an efflux transporter abundantly expressed in the BBB, prevents the accumulation of many drugs in the brain. This study aimed to identify whether five commonly used antidepressants (sertraline, duloxetine, fluoxetine, amitriptyline and mirtazapine) are BCRP substrates. Methods A combination of bidirectional transport and intracellular accumulation experiments was conducted on BCRP-overexpressing MDCKII and wild-type (WT) cells, and in situ brain perfusion was conducted in rats. Key findings The bidirectional transport study revealed that the net efflux ratio (NER) of sertraline reached 2.08 but decreased to 1.06 when co-incubated with Ko143, a selective BCRP inhibitor. Conversely, the other four antidepressants did not appear to be BCRP substrates, due to their low NER values ( Conclusions Taken together, BCRP is involved in sertraline efflux.
- Subjects :
- Abcg2
Amitriptyline
Pharmaceutical Science
Mirtazapine
Pharmacology
Blood–brain barrier
Duloxetine Hydrochloride
030226 pharmacology & pharmacy
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Fluoxetine
Sertraline
medicine
ATP Binding Cassette Transporter, Subfamily G, Member 2
Animals
Humans
030304 developmental biology
0303 health sciences
biology
Chemistry
Brain
Transporter
Biological Transport
Antidepressive Agents
Neoplasm Proteins
Rats
medicine.anatomical_structure
Blood-Brain Barrier
biology.protein
Antidepressant
Efflux
medicine.drug
Subjects
Details
- ISSN :
- 20427158
- Volume :
- 71
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- The Journal of pharmacy and pharmacology
- Accession number :
- edsair.doi.dedup.....b17641b1b6eb701afe97b5f4cb824afc