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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)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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 Volume: 124, Issue: , Pages: 29-33 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Non-patent literature Publications
Reviewing status Peer reviewed