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5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors

The proper pharmacological control of pain is a continuous challenge for patients and health care providers. Even the most widely used medications for pain treatment are still ineffective or unsafe for some patients, especially for those who suffer from chronic pain. Substances containing the chromo...

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Autores principales: Opretzka, Luiza Carolina França, de Freitas, Humberto Fonseca, Espírito-Santo, Renan Fernandes, Abreu, Lucas Silva, Alves, Iura Muniz, Tavares, Josean Fechine, Velozo, Eudes da Silva, Castilho, Marcelo Santos, Villarreal, Cristiane Flora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037321/
https://www.ncbi.nlm.nih.gov/pubmed/33810317
http://dx.doi.org/10.3390/ijms22073413
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author Opretzka, Luiza Carolina França
de Freitas, Humberto Fonseca
Espírito-Santo, Renan Fernandes
Abreu, Lucas Silva
Alves, Iura Muniz
Tavares, Josean Fechine
Velozo, Eudes da Silva
Castilho, Marcelo Santos
Villarreal, Cristiane Flora
author_facet Opretzka, Luiza Carolina França
de Freitas, Humberto Fonseca
Espírito-Santo, Renan Fernandes
Abreu, Lucas Silva
Alves, Iura Muniz
Tavares, Josean Fechine
Velozo, Eudes da Silva
Castilho, Marcelo Santos
Villarreal, Cristiane Flora
author_sort Opretzka, Luiza Carolina França
collection PubMed
description The proper pharmacological control of pain is a continuous challenge for patients and health care providers. Even the most widely used medications for pain treatment are still ineffective or unsafe for some patients, especially for those who suffer from chronic pain. Substances containing the chromone scaffold have shown a variety of biological activities, including analgesic effects. This work presents for the first time the centrally mediated antinociceptive activity of 5-O-methylcneorumchromone K (5-CK). Cold plate and tail flick tests in mice showed that the 5-CK-induced antinociception was dose-dependent, longer-lasting, and more efficacious than that induced by morphine. The 5-CK-induced antinociception was not reversed by the opioid antagonist naloxone. Topological descriptors (fingerprints) were employed to narrow the antagonist selection to further investigate 5-CK’s mechanism of action. Next, based on the results of fingerprints analysis, functional antagonist assays were conducted on nociceptive tests. The effect of 5-CK was completely reversed in both cold plate and tail-flick tests by GABA(A) receptor antagonist bicuculline, but not by atropine or glibenclamide. Molecular docking studies suggest that 5-CK binds to the orthosteric binding site, with a similar binding profile to that observed for bicuculline and GABA. These results evidence that 5-CK has a centrally mediated antinociceptive effect, probably involving the activation of GABAergic pathways.
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spelling pubmed-80373212021-04-12 5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors Opretzka, Luiza Carolina França de Freitas, Humberto Fonseca Espírito-Santo, Renan Fernandes Abreu, Lucas Silva Alves, Iura Muniz Tavares, Josean Fechine Velozo, Eudes da Silva Castilho, Marcelo Santos Villarreal, Cristiane Flora Int J Mol Sci Article The proper pharmacological control of pain is a continuous challenge for patients and health care providers. Even the most widely used medications for pain treatment are still ineffective or unsafe for some patients, especially for those who suffer from chronic pain. Substances containing the chromone scaffold have shown a variety of biological activities, including analgesic effects. This work presents for the first time the centrally mediated antinociceptive activity of 5-O-methylcneorumchromone K (5-CK). Cold plate and tail flick tests in mice showed that the 5-CK-induced antinociception was dose-dependent, longer-lasting, and more efficacious than that induced by morphine. The 5-CK-induced antinociception was not reversed by the opioid antagonist naloxone. Topological descriptors (fingerprints) were employed to narrow the antagonist selection to further investigate 5-CK’s mechanism of action. Next, based on the results of fingerprints analysis, functional antagonist assays were conducted on nociceptive tests. The effect of 5-CK was completely reversed in both cold plate and tail-flick tests by GABA(A) receptor antagonist bicuculline, but not by atropine or glibenclamide. Molecular docking studies suggest that 5-CK binds to the orthosteric binding site, with a similar binding profile to that observed for bicuculline and GABA. These results evidence that 5-CK has a centrally mediated antinociceptive effect, probably involving the activation of GABAergic pathways. MDPI 2021-03-26 /pmc/articles/PMC8037321/ /pubmed/33810317 http://dx.doi.org/10.3390/ijms22073413 Text en © 2021 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Opretzka, Luiza Carolina França
de Freitas, Humberto Fonseca
Espírito-Santo, Renan Fernandes
Abreu, Lucas Silva
Alves, Iura Muniz
Tavares, Josean Fechine
Velozo, Eudes da Silva
Castilho, Marcelo Santos
Villarreal, Cristiane Flora
5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
title 5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
title_full 5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
title_fullStr 5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
title_full_unstemmed 5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
title_short 5-O-methylcneorumchromone K Exerts Antinociceptive Effects in Mice via Interaction with GABAA Receptors
title_sort 5-o-methylcneorumchromone k exerts antinociceptive effects in mice via interaction with gabaa receptors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037321/
https://www.ncbi.nlm.nih.gov/pubmed/33810317
http://dx.doi.org/10.3390/ijms22073413
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