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The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?

Abstract : Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Materials and Methods: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D 1 to D 5 , 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 4 , 5-HT 6 , and 5-HT 7. In vitro autoradiographies using [ 11 C]-Raclopride [ 18 F]-Altanserin [ 18 F]-MPPF [ 11 C]-SB207145, and [ 18 F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate. Results: In cell cultures, the measured Kb confirmed high affinity of loxapine for the D 2 ; intermediate affinity for the D 1 , D 4 , D 5 , 5-HT 2C receptorsl and a lack of affinity toward D 3 , 5-HT 1A , 5-HT 4 , 5-HT 6 , and 5-HT 7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D 2 and 5-HT 2A receptors. Conclusion: This preclinical study reveals that loxapine receptorial spectrum is close to an " atypical " profile (D2/5HT 2A ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification.
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Submitted on : Thursday, June 21, 2018 - 10:26:46 AM
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Florian Ferreri, Dominique Drapier, Emmanuelle Baloche, Mehemed Ouzid, Luc Zimmer, et al.. The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?. International Journal of Neuropsychopharmacology, Oxford University Press (OUP), 2017, 21 (4), pp.355-360. ⟨10.1093/ijnp/pyx102⟩. ⟨hal-01696767⟩

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