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Pharmacopsychiatry 2005; 38(6): 293-300
DOI: 10.1055/s-2005-916184
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Inhibition of P-Glycoprotein Function by Several Antidepressants may not Contribute to Clinical Efficacy

C. C. Weber1 , S. Kressmann1 , M. Ott2 , G. Fricker2 , W. E. Müller1
  • 1Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, Germany
  • 2Institute of Pharmaceutics and Biopharmacy, University of Heidelberg, Heidelberg, Germany
Further Information

Publication History

Received: 15.7.2005 Revised: 15.7.2005

Accepted: 26.7.2005

Publication Date:
08 December 2005 (online)

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Introduction: In many depressive patients the negative feedback mechanism of the HPA (hypothalamic-pituitary-adrenocortical) axis is impaired. It has been suggested that antidepressants inhibit membrane glucocorticoid transporters like P-Glycoprotein (Pgp) and hence enhance the intracellular glucocorticoid concentration, leading to an increased glucocorticoid-receptor mediated gene transcription and therefore to normalization of the function of the HPA axis. The aim of this study is to investigate inhibition of Pgp by several different antidepressants. Methods: We characterized the inhibitory potencies of the antidepressants in two in vitro assays by using calcein-AM as Pgp substrate. The two different cell-systems expressing Pgp were: 1. PBCEC (porcine brain capillary endothelial cells) as model for the blood-brain-barrier, and 2. A human lymphocytic leukaemia cell line CEM and the multi-drug-resistant (MDR) cell line VLB-100, expressing Pgp as model for the human protein. Results: All of the antidepressants tested inhibit the transport of calcein-AM by Pgp in the micromolecular range. Discussion: Because this inhibition is only seen at concentrations above therapeutically relevant plasma levels, their effect my not play a role for the mechanism of action of the antidepressants tested.

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Prof. Dr. W. E. Müller

Department of Pharmacology

Biocenter

Marie-Curie-Str. 9

60439 Frankfurt

Germany

Phone: +69 79829373

Fax: +69 79829374

Email: PharmacolNat@em.uni-frankfurt.de

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