Drug Transport in the Brain

Pharmacotherapy of central nervous system (CNS) disease remains difficult due to limited drug permeation across the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). In addition, brain parenchymal cellular compartments play an important role in regulating CNS drug distribution. This chapter reviews the expression, localization, and functional activity of drug transporters at brain barriers and in brain cellular compartments in normal physiological and pathological conditions. It discusses organic anion-transporting polypeptides (OATPs), organic anion transporters (OATs), organic cation transporters (OCTs), nucleoside transporters (NTs), peptide transporters (PTs), and monocarboxylate transporters (MCTs). The chapter describes relevance of drug transporters in CNS disorders, including brain tumors, epilepsy, neurodegenerative diseases and pain. Nuclear receptors have also been implicated in the regulation of other ATP-binding cassette (ABC) transporters. The dynamic and highly controlled environment of the brain is regulated, in part, by the brain barrier.