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OtherReview Article

Multidrug Resistance-Associated Proteins: Expression and Function in the Central Nervous System

Shannon Dallas, David S. Miller and Reina Bendayan
Pharmacological Reviews June 2006, 58 (2) 140-161; DOI: https://doi.org/10.1124/pr.58.2.3
Shannon Dallas
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (S.D., D.S.M.); and Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada (S.D., R.B.)
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David S. Miller
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (S.D., D.S.M.); and Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada (S.D., R.B.)
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Reina Bendayan
Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina (S.D., D.S.M.); and Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada (S.D., R.B.)
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Abstract

Drug delivery to the brain is highly restricted, since compounds must cross a series of structural and metabolic barriers to reach their final destination, often a cellular compartment such as neurons, microglia, or astrocytes. The primary barriers to the central nervous system are the blood-brain and blood-cerebrospinal fluid barriers. Through structural modifications, including the presence of tight junctions that greatly limit paracellular transport, the cells that make up these barriers restrict diffusion of many pharmaceutically active compounds. In addition, the cells that comprise the blood-brain and blood-cerebrospinal fluid barriers express multiple ATP-dependent, membrane-bound, efflux transporters, such as members of the multidrug resistance-associated protein (MRP) family, which contribute to lowered drug accumulation. A relatively new concept in brain drug distribution just beginning to be explored is the possibility that cellular components of the brain parenchyma could act as a “second” barrier to brain permeation of pharmacological agents via expression of many of the same transporters. Indeed, efflux transporters expressed in brain parenchyma may facilitate the overall export of xenobiotics from the central nervous system, essentially handing themoff to the barrier tissues. We propose that these primary and secondary barriers work in tandem to limit overall accumulation and distribution of xenobiotics in the central nervous system. The present review summarizes recent knowledge in this area and emphasizes the clinical significance of MRP transporter expression in a variety of neurological disorders.

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Pharmacological Reviews: 58 (2)
Pharmacological Reviews
Vol. 58, Issue 2
1 Jun 2006
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OtherReview Article

Multidrug Resistance-Associated Proteins: Expression and Function in the Central Nervous System

Shannon Dallas, David S. Miller and Reina Bendayan
Pharmacological Reviews June 1, 2006, 58 (2) 140-161; DOI: https://doi.org/10.1124/pr.58.2.3

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OtherReview Article

Multidrug Resistance-Associated Proteins: Expression and Function in the Central Nervous System

Shannon Dallas, David S. Miller and Reina Bendayan
Pharmacological Reviews June 1, 2006, 58 (2) 140-161; DOI: https://doi.org/10.1124/pr.58.2.3
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    • Abstract
    • I. Introduction
    • II. The ATP-Binding Cassette Transporter Superfamily
    • III. Multidrug Resistance-Associated Protein Expression and Function in the Central Nervous System
    • IV. Clinical Relevance of Multidrug Resistance-Associated Proteins in the Central Nervous System
    • V. Concluding Remarks
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