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The 5-HT2 antagonist ritanserin blocks dopamine re-uptake in the rat frontal cortex

Molecular Psychiatry volume 5, pages 673–677 (2000)Cite this article

Abstract

The effect of ritanserin on dopamine (DA) re-uptake and efflux was studied in rat frontal cortex synaptosomes. When compared to other 5HT2 receptor antagonists such as ketanserin and risperidone or DA D2 receptor antagonists such as haloperidol and raclopride, the effect of ritanserin proved to be more potent. Ritanserin blocked the DA transporter with a Ki of 0.18 ± 0.06 μM, similar to cocaine (0.11 ± 0.005 μM), while ketanserin had a Ki of 0.93 ± 0.045; haloperidol of 2.07 ± 0.12; risperidone of 18.01 ± 0.62 and raclopride of 24.01 ± 1.55. In addition, 15 min from its local application to the synaptosomes, ritanserin potently released [3]H-DA leaving only 29.6 ± 1.6% of DA content, while ketanserin effect was equal to 46.5 ± 0.9%; haloperidol to 70.4 ± 2.2% and risperidone to 73.9 ± 1.5%, all tested at the dose of 10 μM. Cocaine had no effect on DA efflux. These results suggest that ritanserin has a intrinsic dopaminergic effect which may help to explain its reported improvement on mood, cognition and negative symptoms of schizophrenia.

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Acknowledgements

The present work was partially supported by the European Community, the Italian Government and the Regione Autonoma della Sardegna through the POP Sardegna.

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Authors and Affiliations

  1. Neuroscienze Scarl, Cagliari, 09124-I, Italy

    S Ruiu, G Marchese, G L Gessa & L Pani

  2. ‘BB Brodie’ Dept of Neuroscience, University of Cagliari, Cagliari, 09124-I, Italy

    P L Saba, G L Gessa & L Pani

  3. Center for Neuropharmacology, National Research Council, Cagliari, 09124-I, Italy

    G L Gessa & L Pani

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  1. S Ruiu
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Correspondence to L Pani.

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Ruiu, S., Marchese, G., Saba, P. et al. The 5-HT2 antagonist ritanserin blocks dopamine re-uptake in the rat frontal cortex. Mol Psychiatry 5, 673–677 (2000). https://doi.org/10.1038/sj.mp.4000804

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