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

Molecular Psychiatry volume 7, pages 181–188 (2002)Cite this article

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 μM and 6.0 pmol min−1 mg−1 protein and by monoamine oxidase A 856 μM 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.

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Acknowledgements

This study was supported by the Swiss National Science Foundation (Grants 32–42076.94 and 32–53717.98). We are grateful to Mrs K Powell Golay and to Mr K Dixon, PhD, for the preparation of the manuscript, and to Mrs Eniko Kövari, MD, for collecting brain samples.

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Author notes

  1. M Kosel

    Present address: Psychiatric Neuroimaging Group, Inselspital, Bern, 3010, Switzerland

  2. C Gnerre

    Present address: Biozentrum, Universität Basel, Basel, 4056

  3. P Voirol

    Present address: Dept of Clinical Pharmacy, University of California, San Francisco, 94143, CA, USA

  4. B Rochat

    Present address: Novartis, Basle

Authors and Affiliations

  1. Département Universitaire de Psychiatrie Adulte, Unité de Biochimie et Psychopharmacologie Clinique, Prilly-Lausanne, CH-1008, Switzerland

    M Kosel, P Voirol, M Amey, B Rochat & P Baumann

  2. Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Lausanne, CH-1015, Switzerland

    C Gnerre & B Testa

  3. Département de Psychiatrie, Hôpitaux Universitaires de Genève, Chêne-Bourg, CH-1225, Switzerland

    C Bouras

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Correspondence to P Baumann.

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Kosel, M., Gnerre, C., Voirol, P. et al. In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations. Mol Psychiatry 7, 181–188 (2002). https://doi.org/10.1038/sj.mp.4000946

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