Drugs acting in the CNS must either cross the BBB or the blood-CSF barrier, which are formed by brain capillary endothelial cells or epithelial cells of the choroid plexus, respectively. Efflux transporters play a role in these dynamic barriers. P-glycoprotein extrudes its substrate drugs on the luminal membrane of the brain capillary endothelial cells into the blood, complicating CNS therapy for some drugs (see Chapter 1). Other transporters in the BBB and the blood-CSF barrier include members of organic anion transporting polypeptide (OATP1A4 and OATP1A5) and organic anion transporter (OAT3) families, which facilitate the uptake of organic compounds such as b-lactam antibiotics, statins, PAH, H2-receptor antagonists, and bile acids on the plasma membrane facing the brain-CSF. Further understanding of influx and efflux transporters in these barriers should translate into more effective delivery of drugs to the CNS while avoiding undesirable CNS side effects and may help to define the mechanisms of drug-drug interactions and interindividual differences in the therapeutic CNS effects.
For a complete Bibliographical listing see Goodman & Oilman's The Pharmacological Basis of Therapeutics, 11th ed., or Goodman & Gilman Online at www.accessmedicine.com.
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