Loading...
Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium
Rochat, Bertrand Baumann, Pierre Audus, Kenneth L.
Rochat, Bertrand
Baumann, Pierre
Audus, Kenneth L.
Citations
Altmetric:
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.
Description
Date
1999
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
Antidepressant, Blood-brain barrier, Bovine brain microvessel endothelial cells, Carrier, Enantiomers, P-glycoprotein, Selective serotonin reuptake inhibitor, Stereoselectivity, transport
Citation
Rochat, B., Baumann, P., and Audus, K.L. (1999) Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium. Brain Res. 831, 229-236. PMID: 10412001 http://dx.doi.org/10.1016/S0006-8993(99)01461-4