Region-specific blood-brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer's disease.
Aged, 80 and over
Alzheimer Disease
/ metabolism
Amisulpride
/ pharmacology
Animals
Antipsychotic Agents
/ pharmacology
Binding Sites
Blood-Brain Barrier
/ drug effects
Cell Line
Endothelial Cells
/ drug effects
Female
Haloperidol
/ pharmacology
Humans
Male
Membrane Transport Proteins
/ chemistry
Mice
Mice, Transgenic
Models, Biological
Alzheimer’s
Amisulpride
Blood–brain barrier
MATE1
OCT1
PMAT
Journal
Fluids and barriers of the CNS
ISSN: 2045-8118
Titre abrégé: Fluids Barriers CNS
Pays: England
ID NLM: 101553157
Informations de publication
Date de publication:
17 Dec 2019
17 Dec 2019
Historique:
received:
10
10
2019
accepted:
02
12
2019
entrez:
18
12
2019
pubmed:
18
12
2019
medline:
28
4
2020
Statut:
epublish
Résumé
Research into amisulpride use in Alzheimer's disease (AD) implicates blood-brain barrier (BBB) dysfunction in antipsychotic sensitivity. Research into BBB transporters has been mainly directed towards the ABC superfamily, however, solute carrier (SLC) function in AD has not been widely studied. This study tests the hypothesis that transporters for organic cations contribute to the BBB delivery of the antipsychotics (amisulpride and haloperidol) and is disrupted in AD. The accumulation of [ In vitro BBB and in silico transporter studies indicated that [ Together our research indicates that the increased sensitivity of individuals with Alzheimer's to amisulpride is related to previously unreported changes in function and expression of SLC transporters at the BBB (in particular PMAT and MATE1). Dose adjustments may be required for drugs that are substrates of these transporters when prescribing for individuals with AD.
Sections du résumé
BACKGROUND
BACKGROUND
Research into amisulpride use in Alzheimer's disease (AD) implicates blood-brain barrier (BBB) dysfunction in antipsychotic sensitivity. Research into BBB transporters has been mainly directed towards the ABC superfamily, however, solute carrier (SLC) function in AD has not been widely studied. This study tests the hypothesis that transporters for organic cations contribute to the BBB delivery of the antipsychotics (amisulpride and haloperidol) and is disrupted in AD.
METHODS
METHODS
The accumulation of [
RESULTS
RESULTS
In vitro BBB and in silico transporter studies indicated that [
CONCLUSIONS
CONCLUSIONS
Together our research indicates that the increased sensitivity of individuals with Alzheimer's to amisulpride is related to previously unreported changes in function and expression of SLC transporters at the BBB (in particular PMAT and MATE1). Dose adjustments may be required for drugs that are substrates of these transporters when prescribing for individuals with AD.
Identifiants
pubmed: 31842924
doi: 10.1186/s12987-019-0158-1
pii: 10.1186/s12987-019-0158-1
pmc: PMC6915870
doi:
Substances chimiques
Antipsychotic Agents
0
Membrane Transport Proteins
0
Amisulpride
8110R61I4U
Haloperidol
J6292F8L3D
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
38Subventions
Organisme : Medical Research Council DTP
ID : MR/N013700/1
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L01534X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 080268
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K500811/1
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR/CS/010/019
Pays : United Kingdom
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