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Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice

Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is...

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Autores principales: Żmudzka, Elżbieta, Lustyk, Klaudia, Głuch-Lutwin, Monika, Wolak, Małgorzata, Jaśkowska, Jolanta, Kołaczkowski, Marcin, Sapa, Jacek, Pytka, Karolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967428/
https://www.ncbi.nlm.nih.gov/pubmed/37259325
http://dx.doi.org/10.3390/ph16020175
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author Żmudzka, Elżbieta
Lustyk, Klaudia
Głuch-Lutwin, Monika
Wolak, Małgorzata
Jaśkowska, Jolanta
Kołaczkowski, Marcin
Sapa, Jacek
Pytka, Karolina
author_facet Żmudzka, Elżbieta
Lustyk, Klaudia
Głuch-Lutwin, Monika
Wolak, Małgorzata
Jaśkowska, Jolanta
Kołaczkowski, Marcin
Sapa, Jacek
Pytka, Karolina
author_sort Żmudzka, Elżbieta
collection PubMed
description Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is an urgent need to develop novel multimodal compounds that can be used to treat depression, anxiety, and schizophrenia, as well as memory deficits. Thus, this study aimed to evaluate the potential antidepressant-like, anxiolytic-like, antipsychotic-like effects, and anti-amnesic properties, of the novel arylpiperazine derivative of salicylamide, JJGW07, with an affinity towards serotonin 5-HT(1A), 5-HT(2A), and 5-HT(7) and dopamine D(2) receptors. Firstly, we investigated the compound’s affinity for 5-HT(6) receptors and its functional activity by using in vitro assays. JJGW07 did not bind to 5-HT(6) receptors and showed antagonistic properties for 5-HT(1A), 5-HT(2A), 5-HT(7), and D(2) receptors. Based on the receptor profile, we performed behavioral studies in mice to evaluate the antidepressant-like, anxiolytic-like, and antipsychotic-like activity of the tested compound using forced swim and tail suspension tests; four-plate, marble-burying, and elevated plus maze tests; and MK-801- and amphetamine-induced hyperlocomotion tests, respectively. JJGW07 revealed antidepressant-like properties in the tail suspension test, anxiolytic-like effects in the four-plate and marble-burying tests, and antipsychotic-like activity in the MK-801-induced hyperlocomotion test. Importantly, the tested compound did not induce catalepsy and motor impairments or influence locomotor activity in rodents. Finally, to assess the potential procognitive and anti-amnesic properties of JJGW07, we used passive avoidance and object recognition tests in mice. JJGW07 demonstrated positive effects on long-term emotional memory and also ameliorated MK-801-induced emotional memory impairments in mice, but showed no procognitive properties in the case of recognition memory. Our results encourage the search for new compounds among salicylamide derivatives, which could be model structures with multitarget mechanisms of action that could be used in psychiatric disorder therapy.
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spelling pubmed-99674282023-02-27 Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice Żmudzka, Elżbieta Lustyk, Klaudia Głuch-Lutwin, Monika Wolak, Małgorzata Jaśkowska, Jolanta Kołaczkowski, Marcin Sapa, Jacek Pytka, Karolina Pharmaceuticals (Basel) Article Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is an urgent need to develop novel multimodal compounds that can be used to treat depression, anxiety, and schizophrenia, as well as memory deficits. Thus, this study aimed to evaluate the potential antidepressant-like, anxiolytic-like, antipsychotic-like effects, and anti-amnesic properties, of the novel arylpiperazine derivative of salicylamide, JJGW07, with an affinity towards serotonin 5-HT(1A), 5-HT(2A), and 5-HT(7) and dopamine D(2) receptors. Firstly, we investigated the compound’s affinity for 5-HT(6) receptors and its functional activity by using in vitro assays. JJGW07 did not bind to 5-HT(6) receptors and showed antagonistic properties for 5-HT(1A), 5-HT(2A), 5-HT(7), and D(2) receptors. Based on the receptor profile, we performed behavioral studies in mice to evaluate the antidepressant-like, anxiolytic-like, and antipsychotic-like activity of the tested compound using forced swim and tail suspension tests; four-plate, marble-burying, and elevated plus maze tests; and MK-801- and amphetamine-induced hyperlocomotion tests, respectively. JJGW07 revealed antidepressant-like properties in the tail suspension test, anxiolytic-like effects in the four-plate and marble-burying tests, and antipsychotic-like activity in the MK-801-induced hyperlocomotion test. Importantly, the tested compound did not induce catalepsy and motor impairments or influence locomotor activity in rodents. Finally, to assess the potential procognitive and anti-amnesic properties of JJGW07, we used passive avoidance and object recognition tests in mice. JJGW07 demonstrated positive effects on long-term emotional memory and also ameliorated MK-801-induced emotional memory impairments in mice, but showed no procognitive properties in the case of recognition memory. Our results encourage the search for new compounds among salicylamide derivatives, which could be model structures with multitarget mechanisms of action that could be used in psychiatric disorder therapy. MDPI 2023-01-24 /pmc/articles/PMC9967428/ /pubmed/37259325 http://dx.doi.org/10.3390/ph16020175 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Żmudzka, Elżbieta
Lustyk, Klaudia
Głuch-Lutwin, Monika
Wolak, Małgorzata
Jaśkowska, Jolanta
Kołaczkowski, Marcin
Sapa, Jacek
Pytka, Karolina
Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
title Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
title_full Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
title_fullStr Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
title_full_unstemmed Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
title_short Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice
title_sort novel multimodal salicylamide derivative with antidepressant-like, anxiolytic-like, antipsychotic-like, and anti-amnesic activity in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9967428/
https://www.ncbi.nlm.nih.gov/pubmed/37259325
http://dx.doi.org/10.3390/ph16020175
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