Titre
In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kosel, M.
Auteure/Auteur
Gnerre, C.
Auteure/Auteur
Voirol, P.
Auteure/Auteur
Amey, M.
Auteure/Auteur
Rochat, B.
Auteure/Auteur
Bouras, C.
Auteure/Auteur
Testa, B.
Auteure/Auteur
Baumann, P.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1359-4184
Statut éditorial
Publié
Date de publication
2002
Volume
7
Numéro
2
Première page
181
Dernière page/numéro d’article
188
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
This study was conducted to identify enzyme systems eventually catalysing a local cerebral metabolism of citalopram, a widely used antidepressant of the selective serotonin reuptake inhibitor type. The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria. No cytochrome P-450 mediated transformation was observed in rat brain. By analysing H2O2 formation, monoamine oxidase A activity in rat brain mitochondria could be measured. In rat whole brain and in human frontal cortex, putamen, cerebellum and white matter of five brains monoamine oxidase activity was determined by the stereoselective measurement of the production of citalopram propionate. All substrates were metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B activity could not be detected. Apparent Km and Vmax of S-citalopram biotransformation in human frontal cortex by monoamine oxidase B were found to be 266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856 microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in the same range as those for serotonin and dopamine metabolism by monoamine oxidases. Thus, the biotransformation of citalopram in the rat and human brain occurs mainly through monoamine oxidases and not, as in the liver, through cytochrome P-450.
PID Serval
serval:BIB_4F415C4F4FFF
PMID
Open Access
Oui
Date de création
2008-03-10T09:38:05.076Z
Date de création dans IRIS
2025-05-20T14:43:23Z