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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Donepezil, a cholinesterase inhibitor used in Alzheimer's disease therapy, is actively exported out of the brain by abcb1ab p-glycoproteins in mice.
J. Psychiatr. Res. 124, 29-33 (2020)
Polymorphisms in the drug transporter gene ABCB1 predict the treatment response of selected antidepressants and limit anticonvulsive medication's effectiveness. The ABCB1 locus encodes the energy-dependent transporter P-glycoprotein (P-gp) of the blood brain barrier (BBB), which serves as an efflux pump of its substrates in the expressing tissues of vertebrates. One experimental setup to determine a posteriori the P-gp substrate status is the use of the double abcbl ab knock-out (KO) mice model. Since so far, P-gp substrate status of donepezil, a cholinesterase inhibitor wildly used in Alzheimer's disease therapy was inconclusive, we performed subcutanous (s.c.), continuous injections over 11 days in double abcb1ab KO and P-gp competent wildtype (WT) mice. Both in brain and in testis concentrations of donepezil were significantly higher in P-gp deficient mice compared to WT controls (2.39 and 2.24 times respectively). In conclusion, in mice donepezil's brain bioavailability depends on P-gP.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
3.745
1.310
6
7
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
P-glycoprotein (p-gp) ; Abcb1 ; Blood-brain Barrier ; Donepezil ; Abcb1ab Knock-out Mice; Multidrug-resistance; Species-differences; Gene; Barrier; Penetration; Cyp2d6; Pharmacokinetics; Amitriptyline; Localization; Polymorphism
Sprache
englisch
Veröffentlichungsjahr
2020
HGF-Berichtsjahr
2020
ISSN (print) / ISBN
0022-3956
e-ISSN
1879-1379
Zeitschrift
Journal of Psychiatric Research
Quellenangaben
Band: 124,
Seiten: 29-33
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
WOS ID
WOS:000528204800005
Scopus ID
85080050223
Erfassungsdatum
2020-05-11