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

Overview of attention for article published in The International Journal of Neuropsychopharmacology, November 2013
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Title
Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood–brain barrier permeability
Published in
The International Journal of Neuropsychopharmacology, November 2013
DOI 10.1017/s1461145713000692
Pubmed ID
Authors

Fionn E. O'Brien, Gerard Clarke, Timothy G. Dinan, John F. Cryan, Brendan T. Griffin

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 ≤ 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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 2%
Ireland 1 2%
Unknown 41 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 19%
Student > Master 7 16%
Other 4 9%
Professor > Associate Professor 4 9%
Researcher 3 7%
Other 8 19%
Unknown 9 21%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 8 19%
Agricultural and Biological Sciences 7 16%
Medicine and Dentistry 6 14%
Psychology 3 7%
Veterinary Science and Veterinary Medicine 2 5%
Other 4 9%
Unknown 13 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 October 2013.
All research outputs
#12,084,739
of 13,613,447 outputs
Outputs from The International Journal of Neuropsychopharmacology
#920
of 1,166 outputs
Outputs of similar age
#140,765
of 166,070 outputs
Outputs of similar age from The International Journal of Neuropsychopharmacology
#33
of 56 outputs
Altmetric has tracked 13,613,447 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,166 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 166,070 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 56 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.