Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium

Blood-brain barrier transport of the selective serotonin reuptake inhibitor and antidepressant, citalopram, was studied using monolayers of bovine bra in 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 a s inhibition of metabolizing enzymes of citalopram were investigated. Cital opram transport was saturable and temperature-dependent suggesting that pas sage of the drug across BMECs was mediated by a carrier mechanism. Since th e apical to basolateral and basolateral to apical permeability coefficients were similar and cyclosporin A, a P-glycoprotein inhibitor, does not modif y the transport of citalopram, it appeared that no active efflux systems we re involved in this transport. Citalopram is only available as a racemic dr ug and its pharmacological effect resides mainly in the S-(+)-enantiomer. H owever, the passage of citalopram enantiomers across BMEC monolayers was no t stereoselective. Finally, inhibition of the metabolizing enzymes of cital opram and monoamine oxidases did not modify the permeation of citalopram ac ross BMECs. Collectively, our results suggested that citalopram crosses the blood-brain barrier via a non-stereoselective, bidirectional and symmetric al carrier-mediated mechanism without influences of active efflux mechanism s or monoamine oxidases. (C) 1999 Elsevier Science B.V. All rights reserved .