title: Human ABC transporters at blood-CNS interfaces as determinants of CNS drug penetration.
abstract: Since the discovery of P-glycoprotein (P-gp) in brain microvessels composing the human blood-brain barrier (BBB), ATP-binding 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.
authors.affiliation: Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France|INSERM U705, Neuropsychopharmacologie des addictions, Paris, France|REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
authors.forename: Catarina
authors.initials: C
authors.lastname: Chaves
authors.affiliation: Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France|INSERM U705, Neuropsychopharmacologie des addictions, Paris, France|Department of Pharmacology, Faculty of Medicine & Health Sciences, An-Najah National University, P.O. Box 7, Nablus, Palestine
authors.forename: Ramzi
authors.initials: R
authors.lastname: Shawahna
authors.affiliation: Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France|INSERM U705, Neuropsychopharmacologie des addictions, Paris, France
authors.forename: Aude
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France|INSERM U705, Neuropsychopharmacologie des addictions, Paris, France
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Scherrmann
authors.affiliation: Neuropsychopharmacologie des addictions (CNRS UMR 8206), Université Paris Descartes, Faculté de Pharmacie, Paris, France|INSERM U705, Neuropsychopharmacologie des addictions, Paris, France
authors.forename: Xavier
authors.initials: X
authors.lastname: Declèves
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
chemical_list: D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations