The Role of P-Glycoprotein in Psychiatric Disorders: A Reliable Guard of the Brain?

Onno      L. de Klerk; Fokko      J. Bosker; Gert      Luurtsema; Ilja      M. Nolte; Rudi      Dierckx; Johan      A. den Boer; Heidrun      Potschka

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.

Keywords: P-glycoprotein, blood-brain barrier, major depressive disorder, antidepressive agents, schizophrenia, antipsychotic

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