Increased brain penetration of diphenhydramine and memantine in rats with adjuvant-induced arthritis.
Animals
Antiporters
/ genetics
Arthritis
/ drug therapy
Biological Transport
/ genetics
Blood-Brain Barrier
/ metabolism
Brain
/ drug effects
Cimetidine
/ pharmacology
Diphenhydramine
/ metabolism
Endothelial Cells
/ metabolism
Female
Inflammation
/ drug therapy
Memantine
/ metabolism
Microdialysis
/ methods
Rats
Rats, Sprague-Dawley
Antiporter
Arthritis
Brain
Inflammation
Rat
Transporter
Journal
Brain research
ISSN: 1872-6240
Titre abrégé: Brain Res
Pays: Netherlands
ID NLM: 0045503
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
08
01
2021
revised:
21
05
2021
accepted:
12
07
2021
pubmed:
20
7
2021
medline:
19
3
2022
entrez:
19
7
2021
Statut:
ppublish
Résumé
Brain penetration of cationic drugs is an important determinant of their efficacy and side effects. However, the effects of alterations in the activity of uptake transporters in the brain under inflammatory conditions on the brain penetration of cationic drugs are not fully understood. The aim of this study was to examine changes in brain penetration of cationic drugs, including diphenhydramine (DPHM), memantine (MMT), and cimetidine (CMD), and changes in the expression of uptake transporters such as organic cation transporter (Oct) in brain microvascular endothelial cells (BMECs) under inflammatory conditions. To clarify the effects of inflammation on the brain penetration of DPHM, MMT, and CMD, we performed brain microdialysis studies in a rat model of adjuvant-induced arthritis (AA). Further, differences in transporter mRNA expression levels between BMECs from control and AA rats were evaluated. Brain microdialysis showed that the unbound brain-to-plasma partition coefficient (K
Identifiants
pubmed: 34280372
pii: S0006-8993(21)00438-8
doi: 10.1016/j.brainres.2021.147581
pii:
doi:
Substances chimiques
Antiporters
0
Cimetidine
80061L1WGD
Diphenhydramine
8GTS82S83M
Memantine
W8O17SJF3T
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
147581Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.