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Vol. 53, Issue 4, 569-596, December 2001
Department of Pharmaceutical Sciences, Faculty of Pharmacy,
University of Toronto, Toronto, Ontario, Canada
I. Introduction
II. The Blood-Brain Barrier and the Choroid Plexus
III. Brain Parenchyma
A. Astrocytes
B. Microglia
C. Oligodendrocytes and Neurons
IV. Methods to Quantitate Drug Transport into/out of the
Central Nervous System
In Vivo and In Vitro Methods
A. In Vivo Models to Study Drug Transport across the Blood-brain
Barrier and the Choroid Plexus
B. In Vitro Models to Study Drug Transport in the Brain
V. Drug Transport Mechanisms in the Brain
A. Organic Cation Transport Systems
B. Organic Anion Transport Systems
C. Nucleoside Transport Systems
D. Efflux Transport Systems
1. P-Glycoprotein.
2. Multidrug Resistance Protein Family.
VI. Summary
Acknowledgments
References
Drug transport in the central nervous system is highly regulated not only by the blood-brain and the blood-cerebrospinal fluid barriers but also in brain parenchyma. The novel localization of drug transporters in brain parenchyma cells, such as microglia and astrocytes, suggest a reconsideration of the present conceptualization of brain barriers as it relates to drug transport. That is, the cellular membranes of parenchyma cells act as a second "barrier" to drug permeability and express transporters whose properties appear similar to those localized at the conventional brain barriers. This review will focus on the molecular characteristics, localization, and substrate specificities of several classes of well known membrane drug transporters (i.e., the organic cation, organic anion, nucleoside, P-glycoprotein, and multidrug resistance proteins) in the brain. Comparisons to similar transporters localized within the peripheral system and clinical implications of the functional expression of specific drug transport families will be discussed when appropriate. Nutrient and neurotransmitter transporters, whose characteristics have been reviewed extensively elsewhere, will not be considered in this review.
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