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

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)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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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
ISSN (print) / ISBN 0022-3956
e-ISSN 1879-1379
Quellenangaben Band: 124, Heft: , Seiten: 29-33 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Begutachtungsstatus Peer reviewed