Transport mechanisms for the antidepressant citalopram in brain microvessel endothelium
Issue Date
1999Author
Rochat, Bertrand
Baumann, Pierre
Audus, Kenneth L.
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Metadata
Show full item recordAbstract
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.
Collections
- Pharmacy Scholarly Works [293]
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
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