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- Title
The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
- Authors
Ferreri, Florian; Drapier, Dominique; Baloche, Emmanuelle; Ouzid, Mehemed; Zimmer, Luc; Llorca, Pierre-Michel
- 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 D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145, and [18F]-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 D2; intermediate affinity for the D1, D4, D5, 5-HT2C receptorsl and a lack of affinity toward D3, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors. In brain tissue, PET autoradiographies showed a radiopharmaceutical displacement at low concentrations of loxapine on D2 and 5-HT2A receptors. Conclusion: This preclinical study reveals that loxapine receptorial spectrum is close to an "atypical" profile (D2/5HT2A ratio, 1.14). Loxapine is rightly classified as a DS-RAn agent in the Neuroscience Based Nomenclature classification.
- Subjects
ANTIPSYCHOTIC agents; BIOCHEMICAL mechanism of action; AUTORADIOGRAPHY; CELL culture; RADIOPHARMACEUTICALS
- Publication
International Journal of Neuropsychopharmacology, 2018, Vol 21, Issue 4, p355
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1093/ijnp/pyx102