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Spieler, D. ; Namendorf, C.* ; Namendorf, T.* ; Uhr, M.*

abcb1ab p-glycoprotein is involved in the uptake of the novel antidepressant vortioxetine into the brain of mice.

J. Psychiatr. Res. 109, 48-51 (2019)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
A clinically important and well-studied transporter of the blood-brain barrier (BBB) is P-glycoprotein (P-gp), the gene product of ABCB1. Animal studies have shown that brain concentrations of many antidepressants depend on P-gp, However, biochemical properties, which might allow the prediction of pharmacodynamical involvement of P-gp have not yet been identified, hence thorough experimental testing of each novel drug is needed to determine its P-gp substrate status. In the current study, we tested the P-gp substrate status for the antidepressant vortioxetine using double abcb1ab knock-out (KO) mice. Cerebral concentrations of vortioxetine were 2.3 times higher in P-gp deficient mice compared to wildtype (WT) controls. No significant difference was found regarding the concentration of the drug in the plasma and other organs (liver, kidney, spleen) between KO and WT mice. The results of our study provide conclusive in-vivo evidence that in mice vortioxetine's brain bioavailability is P-gp dependent, expanding previous findings on this topic.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter P-glycoprotein ; Abcb1 ; P-gp ; Blood-brain Barrier ; Vortioxetine ; Knock-out Mice; Multidrug-resistance; Species-differences; Gene; Barrier; Amitriptyline; Penetration; Localization; Transport; Predict; Drugs
Sprache
Veröffentlichungsjahr 2019
Prepublished im Jahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 0022-3956
e-ISSN 1879-1379
Zeitschrift Journal of Psychiatric Research
Quellenangaben Band: 109, Heft: , Seiten: 48-51 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504000-003
DOI 10.1016/j.jpsychires.2018.11.009
WOS ID WOS:000456761200007
Scopus ID 85059248991
PubMed ID 30476727
Erfassungsdatum 2018-12-12
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