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Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate

  • Guillaume Fond
  • Alexandra Macgregor
  • Ryad Tamouza
  • Nora Hamdani
  • Alexandre Meary
  • Marion Leboyer
  • Jean-Francois Dubremetz
Short Communication

Abstract

Recent studies have shown a strong link between Toxoplasma gondii infection and psychiatric disorders, especially schizophrenia and bipolar disorders (odd ratio ≈2.7 for each disorder). Antipsychotic drugs and mood stabilizers may have anti-toxoplasmic activity that potentially may be associated with better effectiveness in these disorders, but previous results have been few in number and conflicting. We therefore sought to determine which daily prescribed antipsychotics and mood stabilizer have the best anti-toxoplasmic activity during the development phase of the parasite. In the present study, we examined the effects of commonly used antipsychotic drugs (amisulpride, cyamemazine, fluphenazine, haloperidol, levomepromazine, loxapine, olanzapine, risperidone and tiapride) and one mood-stabilizing agent (valproate) on toxoplasmic activity. We replicated that fluphenazine has a high anti-toxoplasmic activity, but it does not seem to be a phenothiazine-specific class effect: indeed, we found that another first-generation antipsychotic, zuclopenthixol, has a high anti-toxoplasmic activity. Valproate, tiapride and amisulpride have no anti-toxoplasmic activity on parasite growth, and the other antipsychotic drugs showed low or intermediate anti-toxoplasmic activity. As it is not possible to know the intracellular concentrations of antipsychotics in the brain, further clinical studies are warranted to determine whether these in vitro findings have potential implications in treatment of toxo-positive patients with schizophrenia. These findings may be potentially relevant for the choice of the first-line antipsychotic drug or mood stabilizer in previously infected patients.

Keywords

Toxoplasma gondii Antipsychotic Mood stabilizer Schizophrenia Calmodulin Phenothiazine 

Notes

Acknowledgments

This work was supported by CHRU Montpellier, INSERM, Assistance Publique—Hôpitaux de Paris, and RTRS Santé Mentale (Fondation Fondamental). We thank Hélène Boudon and Arti Jetshan, fellows in pharmacy, Université Montpellier 1, Montpellier, F-34000, France, for their contribution in experiments.

Conflict of interest

Dr. G. Fond, Dr. A. Macgregor, Pr. M. Leboyer, Pr. R. Tamouza, Dr. N. Hamdani, Dr. A. Meary, and Dr. J. F. Dubremetz declare no conflict of interests in connection with the present study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Guillaume Fond
    • 1
  • Alexandra Macgregor
    • 2
  • Ryad Tamouza
    • 3
  • Nora Hamdani
    • 1
  • Alexandre Meary
    • 1
  • Marion Leboyer
    • 1
  • Jean-Francois Dubremetz
    • 4
  1. 1.Fondation FondaMental Fondation de Coopération Scientifique en Santé Mentale, Eq Psychiatrie Génétique, INSERM U955, DHU Pepsy, Pôle de Psychiatrie du Groupe des Hôpitaux Universitaires de MondorUniversité Paris Est-CréteilCréteilFrance
  2. 2.INSERM U1061, Service Universitaire de Psychiatrie Adulte, Hôpital La ColombièreCHRU de MontpellierMontpellierFrance
  3. 3.Jean Dausset Department and INSERM UMRS 940Hôpital Saint LouisParisFrance
  4. 4.UMR 5235 CNRSUniversité de Montpellier 2MontpellierFrance

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