Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration

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Journal Title, Volume, Page: 
Curr Pharm Des. 2013 Jun 19. [Epub ahead of print]
Year of Publication: 
2013
Authors: 
Catarina Chaves
INSERM U705 CNRS UMR 8206, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006 Paris, France
Ramzi Shawahna
INSERM U705 CNRS UMR 8206, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006 Paris, France
Current Affiliation: 
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine
Aude Jacob
INSERM U705 CNRS UMR 8206, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006 Paris, France
Jean- Michel Scherrmann
INSERM U705 CNRS UMR 8206, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006 Paris, France
Xavier Declèves
INSERM U705 CNRS UMR 8206, Faculté de Pharmacie, 4 avenue de l’Observatoire, 75006 Paris, France
Preferred Abstract (Original): 

Since the discovery of P-glycoprotein (P-gp) in brain microvessels composing the human blood-brain barrier (BBB), ATPbinding cassette (ABC) transporters have been recognized as bottlenecks in the development and delivery of neuropharmaceuticals. ABC transporters are expressed predominately at the plasma luminal membrane of brain capillary endothelial cells. These ABC transporters are responsible for the efflux of their substrates from the endothelial cells to the bloodstream against the concentration gradient and thus limit the entry of some drugs within the central nervous system (CNS). Advanced quantitative molecular biology tools allowed gene and protein quantification of the components of microvessels isolated from different species including human. Recently, positron emission tomography using radiolabelled probes that are substrates of ABC transporters allowed the determination of their functional activity at the human BBB. Here, we summarized new information regarding the relative expression, substrate recognition pattern for CNS drugs and functional activity of ABC transporters that are quantitatively expressed at the human BBB.

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