Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability.

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O'Brien FE, Clarke G, Dinan TG, Cryan JF, Griffin BT

Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability.

Int J Neuropsychopharmacol. 2013 Nov;16(10):2259-72. doi: 10.1017/S1461145713000692. Epub 2013 Aug 9.

PubMed ID

23931269 [ View in PubMed

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Abstract

The pharmacological concept that inhibition of the drug efflux pump P-glycoprotein (P-gp) enhances brain distribution of the antidepressant imipramine in the rat has recently been demonstrated. To determine if these findings are relevant to humans, the present study investigated if imipramine is a transported substrate of human P-gp. Furthermore, additional experiments were carried out to determine if findings in relation to imipramine and human P-gp would apply to other antidepressants from a range of different classes. To this end, bidirectional transport experiments were carried out in the ABCB1-transfected MDCKII-MDR1 cell line. Transported substrates of human P-gp are subjected to net efflux in this system, exhibiting a transport ratio (TR) >/= 1.5, and directional efflux is attenuated by co-incubation of a P-gp inhibitor. Imipramine was identified as a transported substrate of human P-gp (TR = 1.68, attenuated by P-gp inhibition). However, the antidepressants amitriptyline, duloxetine, fluoxetine and mirtazapine were not transported substrates of human P-gp (TR

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Amitriptyline	P-glycoprotein 1	Protein	Humans	Unknown	Substrate	Details