Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium

Details

Serval ID
serval:BIB_7286A599F7EE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium
Journal
Brain Research
Author(s)
Rochat  B., Baumann  P., Audus  K. L.
ISSN
0006-8993 (Print)
Publication state
Published
Issued date
06/1999
Volume
831
Number
1-2
Pages
229-36
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun 12
Abstract
Blood-brain barrier transport of the selective serotonin reuptake inhibitor and antidepressant, citalopram, was studied using monolayers of bovine brain microvessel endothelial cells (BMECs). This study provides for the first time, evidence of a transport mechanism for a selective serotonin reuptake inhibitor (SSRI). Carrier-mediated transport, efflux mechanisms, as well as inhibition of metabolizing enzymes of citalopram were investigated. Citalopram transport was saturable and temperature-dependent suggesting that passage of the drug across BMECs was mediated by a carrier mechanism. Since the apical to basolateral and basolateral to apical permeability coefficients were similar and cyclosporin A, a P-glycoprotein inhibitor, does not modify the transport of citalopram, it appeared that no active efflux systems were involved in this transport. Citalopram is only available as a racemic drug and its pharmacological effect resides mainly in the S-(+)-enantiomer. However, the passage of citalopram enantiomers across BMEC monolayers was not stereoselective. Finally, inhibition of the metabolizing enzymes of citalopram and monoamine oxidases did not modify the permeation of citalopram across BMECs. Collectively, our results suggested that citalopram crosses the blood-brain barrier via a non-stereoselective, bidirectional and symmetrical carrier-mediated mechanism without influences of active efflux mechanisms or monoamine oxidases.
Keywords
Animals Antidepressive Agents, Second-Generation/*pharmacokinetics Biological Transport/drug effects Blood-Brain Barrier/*drug effects Cattle Cells, Cultured Citalopram/*pharmacokinetics Dopamine/pharmacology Endothelium, Vascular/*drug effects Monoamine Oxidase Inhibitors/pharmacology Serotonin/pharmacology Serotonin Uptake Inhibitors/*pharmacokinetics Stereoisomerism Tryptophan/pharmacology
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25/01/2008 8:47
Last modification date
20/08/2019 14:30
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