title: ABC transporters and cytochromes P450 in the human central nervous system: influence on brain pharmacokinetics and contribution to neurodegenerative disorders.
abstract: BACKGROUND
  The identification of xenobiotic metabolizing enzymes (i.e., CYP) and transporters (i.e., ABC transporters) (XMET) in the human brain, including the BBB, raises the question whether these transporters and enzymes have specific functions in brain physiology, neuropharmacology and toxicology.
  
  
  METHODS
  Relevant literature was identified using PubMed search articles published up to March 2010. Search terms included 'ABC transporters and P450 or CYP', 'drug metabolism, effect and toxicity' and 'neurodegenerative disease (Alzheimer and Parkinson diseases)' restricted to the field of 'brain or human brain'.
  
  
  RESULTS
  This review aims to provide a better understanding of XMET functions in the human brain and show their pharmacological importance for improving drug delivery and efficacy and also for managing their side effects. Finally, the impact of brain XMET activity during neurodegenerative processes is discussed, giving an opportunity to identify new markers of human brain diseases.
  
  
  CONCLUSIONS
  During the last 2 decades, much evidence concerning the specific distribution patterns of XMET, their induction by xenobiotics and endobiotics and their genetic variations have made cerebral ABC transporters and CYP enzymes key elements in the way individual patients respond to centrally acting drugs.
authors.affiliation: Université Paris Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Dutheil
authors.forename: Aude
authors.initials: A
authors.lastname: Jacob
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dauchy
authors.forename: Philippe
authors.initials: P
authors.lastname: Beaune
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Scherrmann
authors.forename: Xavier
authors.initials: X
authors.lastname: Declèves
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Loriot
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology; D015262:Xenobiotics / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System