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HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats

Anxiety is a common mental disorder, and its prevalence has lately increased because of the COVID-19 pandemic. Unfortunately, the available anxiolytics are often ineffective, and most possess addictive potential. Thus, searching for novel compounds is essential. In our previous studies, we selected...

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Autores principales: Lustyk, Klaudia, Sałaciak, Kinga, Jakubczyk, Magdalena, Jastrzębska-Więsek, Magdalena, Partyka, Anna, Wesołowska, Anna, Marona, Henryk, Pytka, Karolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644393/
https://www.ncbi.nlm.nih.gov/pubmed/36350432
http://dx.doi.org/10.1007/s11064-022-03802-x
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author Lustyk, Klaudia
Sałaciak, Kinga
Jakubczyk, Magdalena
Jastrzębska-Więsek, Magdalena
Partyka, Anna
Wesołowska, Anna
Marona, Henryk
Pytka, Karolina
author_facet Lustyk, Klaudia
Sałaciak, Kinga
Jakubczyk, Magdalena
Jastrzębska-Więsek, Magdalena
Partyka, Anna
Wesołowska, Anna
Marona, Henryk
Pytka, Karolina
author_sort Lustyk, Klaudia
collection PubMed
description Anxiety is a common mental disorder, and its prevalence has lately increased because of the COVID-19 pandemic. Unfortunately, the available anxiolytics are often ineffective, and most possess addictive potential. Thus, searching for novel compounds is essential. In our previous studies, we selected a multimodal compound, HBK-15, which showed a fast antidepressant-like effect in animal models of depression. HBK-15 demonstrated a high affinity for serotonin 5-HT(1A) receptors and moderate for 5-HT(7), dopamine D(2), and α(1)-adrenoceptors. Based on the receptor profile and preliminary studies, we aimed to investigate the anxiolytic potential of HBK-15 using the conditioned-response rat model of anxiety, i.e., the Vogel drinking test. We performed hot plate and free-drinking tests to exclude false positive results in the Vogel test. Using radioligand binding studies, we also investigated the affinity of the compound for the selected biological targets, which play a role in anxiety. Our experiments revealed that HBK-15 showed an anxiolytic-like effect in rats (5 mg/kg) without influencing the pain threshold or the amount of water consumed in the free-drinking test. Furthermore, the tested compound did not show a significant affinity for the selected biological targets, which suggests that its anxiolytic-like mechanism of action could be connected with the interaction with other receptors. This study indicates that multimodal compounds with a receptor profile similar to HBK-15 could be an attractive therapeutic option for patients with a generalized anxiety disorder. However, more studies are required to determine the exact mechanism of action of HBK-15 and its safety profile.
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spelling pubmed-96443932022-11-14 HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats Lustyk, Klaudia Sałaciak, Kinga Jakubczyk, Magdalena Jastrzębska-Więsek, Magdalena Partyka, Anna Wesołowska, Anna Marona, Henryk Pytka, Karolina Neurochem Res Original Paper Anxiety is a common mental disorder, and its prevalence has lately increased because of the COVID-19 pandemic. Unfortunately, the available anxiolytics are often ineffective, and most possess addictive potential. Thus, searching for novel compounds is essential. In our previous studies, we selected a multimodal compound, HBK-15, which showed a fast antidepressant-like effect in animal models of depression. HBK-15 demonstrated a high affinity for serotonin 5-HT(1A) receptors and moderate for 5-HT(7), dopamine D(2), and α(1)-adrenoceptors. Based on the receptor profile and preliminary studies, we aimed to investigate the anxiolytic potential of HBK-15 using the conditioned-response rat model of anxiety, i.e., the Vogel drinking test. We performed hot plate and free-drinking tests to exclude false positive results in the Vogel test. Using radioligand binding studies, we also investigated the affinity of the compound for the selected biological targets, which play a role in anxiety. Our experiments revealed that HBK-15 showed an anxiolytic-like effect in rats (5 mg/kg) without influencing the pain threshold or the amount of water consumed in the free-drinking test. Furthermore, the tested compound did not show a significant affinity for the selected biological targets, which suggests that its anxiolytic-like mechanism of action could be connected with the interaction with other receptors. This study indicates that multimodal compounds with a receptor profile similar to HBK-15 could be an attractive therapeutic option for patients with a generalized anxiety disorder. However, more studies are required to determine the exact mechanism of action of HBK-15 and its safety profile. Springer US 2022-11-09 2023 /pmc/articles/PMC9644393/ /pubmed/36350432 http://dx.doi.org/10.1007/s11064-022-03802-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Lustyk, Klaudia
Sałaciak, Kinga
Jakubczyk, Magdalena
Jastrzębska-Więsek, Magdalena
Partyka, Anna
Wesołowska, Anna
Marona, Henryk
Pytka, Karolina
HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
title HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
title_full HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
title_fullStr HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
title_full_unstemmed HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
title_short HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
title_sort hbk-15, a multimodal compound, showed an anxiolytic-like effect in rats
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644393/
https://www.ncbi.nlm.nih.gov/pubmed/36350432
http://dx.doi.org/10.1007/s11064-022-03802-x
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