Region-specific blood-brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer's disease.

ABSTRACT:

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

The accumulation of [³H]amisulpride (3.7-7.7 nM) and [³H]haloperidol (10 nM) in human (hCMEC/D3) and mouse (bEnd.3) brain endothelial cell lines was explored. Computational approaches examined molecular level interactions of both drugs with the SLC transporters [organic

SUBMITTER: Sekhar GN 

PROVIDER: S-EPMC6915870 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature