Pharmacophore-based discovery of inhibitors of a novel drug/proton antiporter in human brain endothelial hCMEC/D3 cell line.

ABSTRACT:

Background and purpose

An influx drug/proton antiporter of unknown structure has been functionally demonstrated at the blood-brain barrier. This transporter, which handles some psychoactive drugs like diphenhydramine, clonidine, oxycodone, nicotine and cocaine, could represent a new pharmacological target in drug addiction therapy. However, at present there are no known drugs/inhibitors that effectively inhibit/modulate this transporter in vivo.

Experimental approach

The FLAPpharm approach was used to establish a pharmacophore model for inhibitors of this transporter. The inhibitory potency of 44 selected compounds was determined against the specific substrate, [(3)H]-clonidine, in the human cerebral endothelial cell line hCMEC/D3 and ranked as good, medium, weak or non-inhi

SUBMITTER: Chapy H 

PROVIDER: S-EPMC4621989 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature