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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.

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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

Journal Journal of Psychiatric Research

Quellenangaben Volume: 124, Pages: 29-33

Publisher Elsevier

Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)