Table of Contents
ISRN Pharmacology
Volume 2013, Article ID 792456, 5 pages
Research Article

Comparative Cytochrome P450 In Vitro Inhibition by Atypical Antipsychotic Drugs

Department of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, Av. Elvas s/n, 06071 Badajoz, Spain

Received 19 December 2012; Accepted 8 January 2013

Academic Editors: K. Cimanga, G. Froldi, D. K. Miller, R. Villalobos-Molina, and T. B. Vree

Copyright © 2013 Guillermo Gervasini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity ( μM), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of -hydroxybufuralol (IC50 range, 3.5–25.5 μM). Olanzapine inhibited CYP3A-catalyzed production of , and -hydroxymidazolam ( and 42.20 μM, resp.). In contrast, risperidone ( μM) and levomepromazine ( μM) showed selectivity towards the inhibition of midazolam -hydroxylation reaction, and haloperidol did so towards -hydroxylation (IC50 of 2.76 μM). Thioridazine displayed a of 1.75 μM and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce in vivo interactions. However, with this exception, and given the observed values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms in vivo seems limited.