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dc.contributor.authorRochat, Bertrand
dc.contributor.authorBaumann, Pierre
dc.contributor.authorAudus, Kenneth L.
dc.date.accessioned2011-05-23T14:21:34Z
dc.date.available2011-05-23T14:21:34Z
dc.date.issued1999
dc.identifier.citationRochat, 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
dc.identifier.urihttp://hdl.handle.net/1808/7489
dc.description.abstractBlood-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.
dc.language.isoen_US
dc.publisherElsevier
dc.subjectAntidepressant
dc.subjectBlood-brain barrier
dc.subjectBovine brain microvessel endothelial cells
dc.subjectCarrier
dc.subjectEnantiomers
dc.subjectP-glycoprotein
dc.subjectSelective serotonin reuptake inhibitor
dc.subjectStereoselectivity
dc.subjecttransport
dc.titleTransport mechanisms for the antidepressant citalopram in brain microvessel endothelium
dc.typeArticle
kusw.kuauthorAudus, Kenneth L.
kusw.kudepartmentSchool of Pharmacy
kusw.oastatusfullparticipation
dc.identifier.doi10.1016/S0006-8993(99)01461-4
kusw.oaversionScholarly/refereed, author accepted manuscript
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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