Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity
In this work, we describe a new route for the synthesis and the antinociceptive effects of two new <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides (named C<sub>20:0</sub>-5HT and C<sub>22:0</sub>-5HT). The antinociceptive activities were evaluated u...
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MDPI AG
2021-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/5/455 |
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| author | Jorge Luis Amorim Fernanda Alves Lima Ana Laura Macedo Brand Silvio Cunha Claudia Moraes Rezende Patricia Dias Fernandes |
| author_facet | Jorge Luis Amorim Fernanda Alves Lima Ana Laura Macedo Brand Silvio Cunha Claudia Moraes Rezende Patricia Dias Fernandes |
| author_sort | Jorge Luis Amorim |
| collection | DOAJ |
| description | In this work, we describe a new route for the synthesis and the antinociceptive effects of two new <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides (named C<sub>20:0</sub>-5HT and C<sub>22:0</sub>-5HT). The antinociceptive activities were evaluated using well-known models of thermal-induced (reaction to a heated plate, the hot plate model) or chemical-induced (licking response to paw injection of formalin, capsaicin, or glutamate) nociception. The mechanism of action for C<sub>20:0</sub>-5HT and C<sub>22:0</sub>-5HT was evaluated using naloxone (opioid receptor antagonist, 1 mg/kg), atropine (muscarinic receptor antagonist, 1 mg/kg), AM251 (cannabinoid CB1 receptor antagonist, 1 mg/kg), or ondansetron (5-HT3 serotoninergic receptor antagonist, 0.5 mg/kg) 30 min prior to C<sub>20:0</sub>-5HT or C<sub>22:0</sub>-5HT. The substances both presented significant effects by reducing licking behavior induced by formalin, capsaicin, and glutamate and increasing the latency time in the hot plate model. Opioidergic, muscarinic, cannabinoid, and serotoninergic pathways seem to be involved in the antinociceptive activity since their antagonists reversed the observed effect. Opioid receptors are partially involved due to tolerant mice demonstrating less antinociception when treated with both compounds. Our data showed a quicker and simpler route for the synthesis of the new <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides. Both compounds demonstrated significant antinociceptive effects. These new compounds could be used as a scaffold for the synthesis of analogues with promising antinociceptive effects. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T12:04:39Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-4f6c2f86d6a44e9abe7f2c4929147e042023-11-21T16:40:42ZengMDPI AGBiomedicines2227-90592021-04-019545510.3390/biomedicines9050455Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive ActivityJorge Luis Amorim0Fernanda Alves Lima1Ana Laura Macedo Brand2Silvio Cunha3Claudia Moraes Rezende4Patricia Dias Fernandes5Laboratório de Farmacologia da Dor e da Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilCentro de Tecnologia, Laboratório de Análise de Aromas, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilCentro de Tecnologia, Laboratório de Análise de Aromas, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilGrupo de Pesquisa em Síntese Química e Bioatividade Molecular, Instituto de Química, Universidade Federal da Bahia, Salvador 40170-115, BrazilCentro de Tecnologia, Laboratório de Análise de Aromas, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, BrazilLaboratório de Farmacologia da Dor e da Inflamação, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilIn this work, we describe a new route for the synthesis and the antinociceptive effects of two new <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides (named C<sub>20:0</sub>-5HT and C<sub>22:0</sub>-5HT). The antinociceptive activities were evaluated using well-known models of thermal-induced (reaction to a heated plate, the hot plate model) or chemical-induced (licking response to paw injection of formalin, capsaicin, or glutamate) nociception. The mechanism of action for C<sub>20:0</sub>-5HT and C<sub>22:0</sub>-5HT was evaluated using naloxone (opioid receptor antagonist, 1 mg/kg), atropine (muscarinic receptor antagonist, 1 mg/kg), AM251 (cannabinoid CB1 receptor antagonist, 1 mg/kg), or ondansetron (5-HT3 serotoninergic receptor antagonist, 0.5 mg/kg) 30 min prior to C<sub>20:0</sub>-5HT or C<sub>22:0</sub>-5HT. The substances both presented significant effects by reducing licking behavior induced by formalin, capsaicin, and glutamate and increasing the latency time in the hot plate model. Opioidergic, muscarinic, cannabinoid, and serotoninergic pathways seem to be involved in the antinociceptive activity since their antagonists reversed the observed effect. Opioid receptors are partially involved due to tolerant mice demonstrating less antinociception when treated with both compounds. Our data showed a quicker and simpler route for the synthesis of the new <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides. Both compounds demonstrated significant antinociceptive effects. These new compounds could be used as a scaffold for the synthesis of analogues with promising antinociceptive effects.https://www.mdpi.com/2227-9059/9/5/455serotonin amides<sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamidesantinociceptive activitypainmechanochemical synthesis |
| spellingShingle | Jorge Luis Amorim Fernanda Alves Lima Ana Laura Macedo Brand Silvio Cunha Claudia Moraes Rezende Patricia Dias Fernandes Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity Biomedicines serotonin amides <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides antinociceptive activity pain mechanochemical synthesis |
| title | Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity |
| title_full | Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity |
| title_fullStr | Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity |
| title_full_unstemmed | Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity |
| title_short | Two New <sup>β</sup><i>N</i>-Alkanoyl-5-Hydroxytryptamides with Relevant Antinociceptive Activity |
| title_sort | two new sup β sup i n i alkanoyl 5 hydroxytryptamides with relevant antinociceptive activity |
| topic | serotonin amides <sup>β</sup><i>N</i>-alkanoyl-5-hydroxytryptamides antinociceptive activity pain mechanochemical synthesis |
| url | https://www.mdpi.com/2227-9059/9/5/455 |
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