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Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models

The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxy)ethoxy]ethyl}-4-(2-methoxyphenyl)piperazynine hydrochloride (HBK-14) and 2-[2-(2-chloro-6-methylphenoxy)ethoxy]ethyl-4-(2- methoxyphenyl)piperazynine dihydroc...

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Autores principales: Pytka, Karolina, Partyka, Anna, Jastrzębska-Więsek, Magdalena, Siwek, Agata, Głuch-Lutwin, Monika, Mordyl, Barbara, Kazek, Grzegorz, Rapacz, Anna, Olczyk, Adrian, Gałuszka, Adam, Błachuta, Marian, Waszkielewicz, Anna, Marona, Henryk, Sapa, Jacek, Filipek, Barbara, Wesołowska, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640659/
https://www.ncbi.nlm.nih.gov/pubmed/26554929
http://dx.doi.org/10.1371/journal.pone.0142499
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author Pytka, Karolina
Partyka, Anna
Jastrzębska-Więsek, Magdalena
Siwek, Agata
Głuch-Lutwin, Monika
Mordyl, Barbara
Kazek, Grzegorz
Rapacz, Anna
Olczyk, Adrian
Gałuszka, Adam
Błachuta, Marian
Waszkielewicz, Anna
Marona, Henryk
Sapa, Jacek
Filipek, Barbara
Wesołowska, Anna
author_facet Pytka, Karolina
Partyka, Anna
Jastrzębska-Więsek, Magdalena
Siwek, Agata
Głuch-Lutwin, Monika
Mordyl, Barbara
Kazek, Grzegorz
Rapacz, Anna
Olczyk, Adrian
Gałuszka, Adam
Błachuta, Marian
Waszkielewicz, Anna
Marona, Henryk
Sapa, Jacek
Filipek, Barbara
Wesołowska, Anna
author_sort Pytka, Karolina
collection PubMed
description The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxy)ethoxy]ethyl}-4-(2-methoxyphenyl)piperazynine hydrochloride (HBK-14) and 2-[2-(2-chloro-6-methylphenoxy)ethoxy]ethyl-4-(2- methoxyphenyl)piperazynine dihydrochloride (HBK-15) in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST) in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM) in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT(2), adrenergic α(1), and dopaminergic D(2) receptors as well as being full 5-HT(1A) and 5-HT(7) receptor antagonists. We also present their potent antidepressant-like activity (HBK-14—FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg) and (HBK-15—FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg). We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg) and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg) possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT(1A) receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds.
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spelling pubmed-46406592015-11-13 Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models Pytka, Karolina Partyka, Anna Jastrzębska-Więsek, Magdalena Siwek, Agata Głuch-Lutwin, Monika Mordyl, Barbara Kazek, Grzegorz Rapacz, Anna Olczyk, Adrian Gałuszka, Adam Błachuta, Marian Waszkielewicz, Anna Marona, Henryk Sapa, Jacek Filipek, Barbara Wesołowska, Anna PLoS One Research Article The aim of this study was to further characterize pharmacological properties of two phenylpiperazine derivatives: 1-{2-[2-(2,6-dimethlphenoxy)ethoxy]ethyl}-4-(2-methoxyphenyl)piperazynine hydrochloride (HBK-14) and 2-[2-(2-chloro-6-methylphenoxy)ethoxy]ethyl-4-(2- methoxyphenyl)piperazynine dihydrochloride (HBK-15) in radioligand binding and functional in vitro assays as well as in vivo models. Antidepressant-like properties were investigated in the forced swim test (FST) in mice and rats. Anxiolytic-like activity was evaluated in the four-plate test in mice and elevated plus maze test (EPM) in rats. Imipramine and escitalopram were used as reference drugs in the FST, and diazepam was used as a standard anxiolytic drug in animal models of anxiety. Our results indicate that HBK-14 and HBK-15 possess high or moderate affinity for serotonergic 5-HT(2), adrenergic α(1), and dopaminergic D(2) receptors as well as being full 5-HT(1A) and 5-HT(7) receptor antagonists. We also present their potent antidepressant-like activity (HBK-14—FST mice: 2.5 and 5 mg/kg; FST rats: 5 mg/kg) and (HBK-15—FST mice: 1.25, 2.5 and 5 mg/kg; FST rats: 1.25 and 2.5 mg/kg). We show that HBK-14 (four-plate test: 2.5 and 5 mg/kg; EPM: 2.5 mg/kg) and HBK-15 (four-plate test: 2.5 and 5 mg/kg; EPM: 5 mg/kg) possess anxiolytic-like properties. Among the two, HBK-15 has stronger antidepressant-like properties, and HBK-14 displays greater anxiolytic-like activity. Lastly, we demonstrate the involvement of serotonergic system, particularly 5-HT(1A) receptor, in the antidepressant- and anxiolytic-like actions of investigated compounds. Public Library of Science 2015-11-10 /pmc/articles/PMC4640659/ /pubmed/26554929 http://dx.doi.org/10.1371/journal.pone.0142499 Text en © 2015 Pytka et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pytka, Karolina
Partyka, Anna
Jastrzębska-Więsek, Magdalena
Siwek, Agata
Głuch-Lutwin, Monika
Mordyl, Barbara
Kazek, Grzegorz
Rapacz, Anna
Olczyk, Adrian
Gałuszka, Adam
Błachuta, Marian
Waszkielewicz, Anna
Marona, Henryk
Sapa, Jacek
Filipek, Barbara
Wesołowska, Anna
Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models
title Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models
title_full Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models
title_fullStr Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models
title_full_unstemmed Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models
title_short Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT(1A) and 5-HT(7) Antagonists in Animal Models
title_sort antidepressant- and anxiolytic-like effects of new dual 5-ht(1a) and 5-ht(7) antagonists in animal models
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640659/
https://www.ncbi.nlm.nih.gov/pubmed/26554929
http://dx.doi.org/10.1371/journal.pone.0142499
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