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

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)...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferreri, Florian, Drapier, Dominique, Baloche, Emmanuelle, Ouzid, Mehemed, Zimmer, Luc, Llorca, Pierre-Michel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Brief Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887516/
https://www.ncbi.nlm.nih.gov/pubmed/29106549
http://dx.doi.org/10.1093/ijnp/pyx102
_version_ 1783312321237483520
author Ferreri, Florian
Drapier, Dominique
Baloche, Emmanuelle
Ouzid, Mehemed
Zimmer, Luc
Llorca, Pierre-Michel
author_facet Ferreri, Florian
Drapier, Dominique
Baloche, Emmanuelle
Ouzid, Mehemed
Zimmer, Luc
Llorca, Pierre-Michel
author_sort Ferreri, Florian
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5887516
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-58875162018-04-11 The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug? Ferreri, Florian Drapier, Dominique Baloche, Emmanuelle Ouzid, Mehemed Zimmer, Luc Llorca, Pierre-Michel Int J Neuropsychopharmacol Brief Report 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. Oxford University Press 2017-11-02 /pmc/articles/PMC5887516/ /pubmed/29106549 http://dx.doi.org/10.1093/ijnp/pyx102 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Brief Report
Ferreri, Florian
Drapier, Dominique
Baloche, Emmanuelle
Ouzid, Mehemed
Zimmer, Luc
Llorca, Pierre-Michel
The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
title The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
title_full The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
title_fullStr The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
title_full_unstemmed The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
title_short The in Vitro Actions of Loxapine on Dopaminergic and Serotonergic Receptors. Time to Consider Atypical Classification of This Antipsychotic Drug?
title_sort in vitro actions of loxapine on dopaminergic and serotonergic receptors. time to consider atypical classification of this antipsychotic drug?
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887516/
https://www.ncbi.nlm.nih.gov/pubmed/29106549
http://dx.doi.org/10.1093/ijnp/pyx102
work_keys_str_mv AT ferreriflorian theinvitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT drapierdominique theinvitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT balocheemmanuelle theinvitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT ouzidmehemed theinvitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT zimmerluc theinvitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT llorcapierremichel theinvitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT ferreriflorian invitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT drapierdominique invitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT balocheemmanuelle invitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT ouzidmehemed invitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT zimmerluc invitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug
AT llorcapierremichel invitroactionsofloxapineondopaminergicandserotonergicreceptorstimetoconsideratypicalclassificationofthisantipsychoticdrug

Ejemplares similares