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A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian)

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Abstract

Rationale

Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT2A receptors, which was fourfold higher than its affinity for dopamine D2 receptors (Hameg et al. 2003).

Objectives

The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian.

Methods

Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D2 and serotonin 5-HT2A receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [11C]raclopride and [11C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan.

Results

Cyamemazine induced near saturation of 5-HT2A receptors (RO=62.1–98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D2 receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2–74.9%). The effective plasma level of cyamemazine leading to 50% of D2 receptor occupancy was fourfold higher than that for 5-HT2A receptors. Accordingly, individual 5-HT2A/D2 RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale.

Conclusion

This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT2A receptors compared to dopamine D2 receptors. In the dose range 37.5–300 mg, levels of dopamine D2 occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.

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Acknowledgements

We thank H.-J. Machulla for his help in radiotracer preparations, B.M. Dohmen for the administrative management at the PET site, M.-P. Thomas for her clinical research assistance, C. Staner for healthy volunteer management and C. Ziegler for patient management.

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Authors and Affiliations

  1. FORENAP Research Institute For Neuroscience, Pharmacology and Psychiatry, 68250, Rouffach, France

    Y. Hodé, A. Demazières & J. P. Macher

  2. Department of Nuclear Medicine, Tübingen University Hospital, 72076, Tübingen, Germany

    M. Reimold

  3. Radiopharmacy, University of Tübingen, 72076, Tübingen, Germany

    G. Reischl

  4. INSERM EMI-E0117, Université Paris V, 75014, Paris, France

    F. Bayle

  5. Hôpital Saint Antoine, 75571, Paris Cedex 12, France

    P. Nuss

  6. Aventis, 46 Quai de la rapée, 75601, Paris Cedex 12, France

    A. Hameg & M. Dib

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  1. Y. Hodé
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Correspondence to Y. Hodé.

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Hodé, Y., Reimold, M., Demazières, A. et al. A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine 5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian). Psychopharmacology 180, 377–384 (2005). https://doi.org/10.1007/s00213-005-2172-z

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  • DOI: https://doi.org/10.1007/s00213-005-2172-z

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