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

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Abstract

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) â© 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 â© 1.16 in all cases). These results offer insight into the role of P-gp in the distribution of antidepressants, revealing that rodent findings pertaining to imipramine may translate to humans. Moreover, the present results highlight that other antidepressants may not be transported substrates of human P-gp. © CINP 2013.

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APA

O’Brien, F. E., Clarke, G., Dinan, T. G., Cryan, J. F., & Griffin, B. T. (2013). Human P-glycoprotein differentially affects antidepressant drug transport: Relevance to blood-brain barrier permeability. In International Journal of Neuropsychopharmacology (Vol. 16, pp. 2259–2272). https://doi.org/10.1017/S1461145713000692

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