Abstract：
:The ability to overcome cellular barriers in the body is crucial for efficient delivery of drugs to the target where intervention is needed. For drugs acting in the brain it is essential to overcome the blood-brain barrier (BBB). Such drugs include antidotes for the treatment of organophosphate poisoning, a current warfare and terroristic threat. Being lipophilic compounds, organophosphates readily penetrate the brain and block the enzyme acetylcholinesterase (AChE). They cause severe symptoms which may have fatal consequences. A major drawback of currently available oxime reactivators is their inability to reactivate AChE in the central nervous system (CNS) as they are unable to cross the blood-brain barrier. An important obstacle preventing many drugs from reaching their therapeutic target in the brain is the efflux transporter P-glycoprotein (P-gp), whose function is to prevent the penetration of potentially harmful substances. The aim of this study was to evaluate the effect of P-gp on the permeation of oximes into the brain. The study of this interaction was carried out on the CACO-2 cell line, stably expressing P-gp. As it turned out, P-gp has no essential influence on the central availability of clinically used oxime reactivators within this study.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Kobrlova T,Soukup Odoi
10.1016/j.tox.2020.152541subject
Has Abstractpub_date
2020-10-01 00:00:00pages
152541eissn
0300-483Xissn
1879-3185pii
S0300-483X(20)30180-3journal_volume
443pub_type
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