title: Overview of experimental models of the blood-brain barrier in CNS drug discovery.
abstract: The blood-brain barrier (BBB) is a physical and metabolic entity that isolates the brain from the systemic circulation. The barrier consists of tight junctions between endothelial cells that contain egress transporters and catabolic enzymes. To cross the BBB, a drug must possess the appropriate physicochemical properties to achieve a sufficient time-concentration profile in brain interstitial fluid (ISF). In this overview, we review techniques to measure BBB permeation, which is evidenced by the free concentration of compound in brain ISF over time. We consider a number of measurement techniques, including in vivo microdialysis and brain receptor occupancy following perfusion. Consideration is also given to the endothelial and nonendothelial cell systems used to assess both the BBB permeation of a test compound and its interactions with egress transporters, and computer models employed for predicting passive permeation and the probability of interactions with BBB transporters.
authors: Cerebroscience, London, United Kingdom.
authors: Alan M
authors: AM
authors: Palmer
authors: Pharmidex Pharmaceutical Services, London, United Kingdom.
authors: Mohammad S
authors: MS
authors: Alavijeh
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000145:classification / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000502:physiology; D008954:Models, Biological; D010539:Permeability / Q000187:drug effects; D011955:Receptors, Drug / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D002491:Central Nervous System Agents; D011955:Receptors, Drug
keywords: MDCK cells; blood-brain barrier; brain disorders; brain medicines; drug discovery; in vivo microdialysis; neuroscience; receptor occupancy