Drug transporters in the central nervous system

Clin Pharmacokinet. 2015 Mar;54(3):225-42. doi: 10.1007/s40262-015-0241-y.

Abstract

Drug targets in the central nervous system (CNS) are numerous and important for drug therapy, e.g., of epilepsy or pain. Drugs and other xenobiotics as well as nutrients cannot freely cross the blood-brain barrier or freely enter cells across plasma membranes and therefore require transport systems. This overview summarizes the current knowledge on the expression of drug transporters in barriers shielding the CNS from the systemic circulation and as such controlling the pharmacokinetics of drugs in the CNS. The main drug transporter families covered are SLCO, SCL22A, ABCB, and ABCC, as genes of these families code for numerous drug transporters. While knowledge on messenger RNA expression in humans, rats, and mice is remarkable, there is clearly a gap in knowledge on the subcellular expression of transporters in specific cells in the CNS and in the barriers shielding the CNS from the systemic circulation. Recent methodologic developments including synthesis of drugs and endogenous substances for imaging will in the future allow the investigation of the function and physiologic role of transporters in the CNS including difficult-to-access systems such as the choroid plexus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Blood-Brain Barrier / metabolism
  • Central Nervous System / metabolism*
  • Humans
  • Membrane Transport Proteins / metabolism*
  • Organic Anion Transporters / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Membrane Transport Proteins
  • Organic Anion Transporters