title: The role of p-glycoprotein in psychiatric disorders: a reliable guard of the brain?
abstract: A major component in the protection of the brain against blood-borne toxic influences is the multispecific efflux pump P-glycoprotein. This pump, a 170 kD protein, located at the luminal side of the capillary endothelial cells, has a large capacity and is capable of extruding a wide array of structurally divergent substrates. The brain uptake of the majority of antidepressants and antipsychotics, as well as many other psychotropic drugs and endogenous compounds is hampered by the activity of P-glycoprotein. In this review we discuss the current state of knowledge concerning the role of Pglycoprotein on pharmacokinetics of psychiatric drugs and the impact of modulation of P-glycoprotein on major psychiatric disorders. Relevant issues in reference to the function of P-glycoprotein and other efflux pumps in the blood-brain barrier related to mood disorders and schizophrenia are addressed, such as a possible role of P-glycoprotein as a susceptibility factor in depressive disorders and psychotic disorders.
authors.affiliation: Department of Psychiatry, University Medical Center Groningen (UMCG), The Netherlands. o.l.klerk@ngmb.umcg.nl
authors.forename: Onno L
authors.initials: OL
authors.lastname: De Klerk
authors.forename: Fokko J
authors.initials: FJ
authors.lastname: Bosker
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Nolte
authors.forename: Rudi
authors.initials: R
authors.lastname: Dierckx
authors.forename: Johan A
authors.initials: JA
authors.lastname: Den Boer
authors.forename: Heidrun
authors.initials: H
authors.lastname: Potschka
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D008958:Models, Molecular; D009410:Nerve Degeneration / Q000503:physiopathology; D011619:Psychotropic Drugs / Q000378:metabolism / Q000627:therapeutic use; D013315:Stress, Psychological; D013379:Substrate Specificity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011619:Psychotropic Drugs