In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations

Details

Serval ID
serval:BIB_4F415C4F4FFF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations
Journal
Molecular psychiatry
Author(s)
Kosel M., Gnerre C., Voirol P., Amey M., Rochat B., Bouras C., Testa B., Baumann P.
ISSN
1359-4184
Publication state
Published
Issued date
2002
Peer-reviewed
Oui
Volume
7
Number
2
Pages
181-188
Language
english
Notes
Publication types: In Vitro ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
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.
Keywords
Animals, Brain, Citalopram, Cytochrome P-450 Enzyme System, Humans, Hydrogen Peroxide, Methylation, Mitochondria, Monoamine Oxidase, Rats, Serotonin, Serotonin Uptake Inhibitors, Stereoisomerism
Pubmed
Web of science
Open Access
Yes
Create date
10/03/2008 10:38
Last modification date
20/08/2019 14:05
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