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Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems Tsuji ANeuroRx 2005[Jan]; 2 (1): 54-62Because of the physiological nature of the blood-brain barrier (BBB), transport of chemical compounds between blood and brain has been widely believed to occur by means of passive diffusion, depending upon the lipophilicity of the compounds. However, discrepancies exist between the lipophilicity and apparent BBB permeation properties in many cases, and these discrepancies can be ascribed to the existence of multiple mechanisms of drug transport through the BBB. Molecular identification and functional analysis of influx transport proteins (from blood to brain) and efflux transport proteins (from brain to blood) have progressed rapidly. Therefore, the BBB is now considered to be a dynamic interface that controls the influx and efflux of a wide variety of substances, including endogenous nutrients and exogenous compounds such as drugs, to maintain a favorable environment for the CNS. This review focuses on the role of transport systems in the uptake of xenobiotics, including organic anionic/cationic and neutral drugs, across the BBB into the brain, as well as on strategies to increase drug delivery into the brain by blocking efflux transport protein function, or to reduce CNS side effects by modulating BBB transport processes.|*Blood-Brain Barrier[MESH]|*Drug Carriers[MESH]|Animals[MESH]|Biological Transport, Active[MESH]|Carrier Proteins/*metabolism[MESH]|Central Nervous System Agents/*metabolism[MESH]|Humans[MESH]|Organic Cation Transport Proteins/metabolism[MESH]|Peptides/metabolism[MESH] |
