Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/3835 |
Resumo: | Depression and chronic pain coexist in several patients and may be modulated by the same neurotransmitter systems. In this context, various studies have demonstrated that antidepressants from the class of the inhibitors of monoamine oxidase-A (MAO-A) enzyme presented antinociceptive effect in different pain models in experimental animals, as well as analgesic action in clinic studies. Thus, in the present study were evaluated the MAO-A inhibitory properties, as well as the antidepressant and antinociceptive potential of the novel imidazoline compound 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice. 2-DMPI showed to be a mixed, reversible and preferential MAO-A inhibitor. The treatment with 2-DMPI (100-1000 μmol/kg, s.c.) produced an antidepressant-like effect in the tail suspension test without affecting motor activity of the animals. The mice treated with 2-DMPI showed a decrease in serotonin and dopamine turnover in specific brain regions, suggesting that the antidepressant-like effect of this compound was mediated by serotonergic and dopaminergic systems. This was confirmed by experiments showing that the antidepressant-like effect of 2-DMPI was abolished by pretreatment with serotonergic and dopaminergic receptor antagonists. In order to evaluate a possible antinociceptive action of 2-DMPI, a mice model of neuropathic pain, induced by chronic constriction injury (CCI) of the sciatic nerve was used. It was observed that mice submitted to CCI presented an increase in MAO-A activity in lumbar spinal cord compared with sham-submitted mice and that the treatment with 2-DMPI (30-300 μmol/kg, s.c.) reversed the CCI-induced mechanical hyperalgesia. Furthermore, the antihyperalgesic effect of 2-DMPI was reversed by intrathecal injection of the serotonergic 5-HT3 receptor antagonist ondansetron (10 μg/site). These results suggest that 2-DMPI, due to its ability to modulate MAO-A activity and, consequently, the monoaminergic systems, could be a promising prototype to the development of new drugs with antidepressant and analgesic properties. |
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2013-08-222013-08-222012-12-18VILLARINHO, Jardel Gomes. ANTIDEPRESSANT AND ANALGESIC POTENTIAL OF 2-(3,4-DIMETHOXY-PHENYL)-4,5-DIHYDRO-1H-IMIDAZOLE (2-DMPI) IN MICE. 2012. 92 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/3835Depression and chronic pain coexist in several patients and may be modulated by the same neurotransmitter systems. In this context, various studies have demonstrated that antidepressants from the class of the inhibitors of monoamine oxidase-A (MAO-A) enzyme presented antinociceptive effect in different pain models in experimental animals, as well as analgesic action in clinic studies. Thus, in the present study were evaluated the MAO-A inhibitory properties, as well as the antidepressant and antinociceptive potential of the novel imidazoline compound 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice. 2-DMPI showed to be a mixed, reversible and preferential MAO-A inhibitor. The treatment with 2-DMPI (100-1000 μmol/kg, s.c.) produced an antidepressant-like effect in the tail suspension test without affecting motor activity of the animals. The mice treated with 2-DMPI showed a decrease in serotonin and dopamine turnover in specific brain regions, suggesting that the antidepressant-like effect of this compound was mediated by serotonergic and dopaminergic systems. This was confirmed by experiments showing that the antidepressant-like effect of 2-DMPI was abolished by pretreatment with serotonergic and dopaminergic receptor antagonists. In order to evaluate a possible antinociceptive action of 2-DMPI, a mice model of neuropathic pain, induced by chronic constriction injury (CCI) of the sciatic nerve was used. It was observed that mice submitted to CCI presented an increase in MAO-A activity in lumbar spinal cord compared with sham-submitted mice and that the treatment with 2-DMPI (30-300 μmol/kg, s.c.) reversed the CCI-induced mechanical hyperalgesia. Furthermore, the antihyperalgesic effect of 2-DMPI was reversed by intrathecal injection of the serotonergic 5-HT3 receptor antagonist ondansetron (10 μg/site). These results suggest that 2-DMPI, due to its ability to modulate MAO-A activity and, consequently, the monoaminergic systems, could be a promising prototype to the development of new drugs with antidepressant and analgesic properties.A depressão e a dor coexistem em muitos pacientes e podem ser moduladas pelos mesmos sistemas de neurotransmissores. Nesse contexto, diversos estudos têm demonstrado que antidepressivos da classe dos inibidores da enzima monoamina oxidase-A (MAO-A) apresentam efeito antinociceptivo em diferentes modelos de dor em animais experimentais, assim como ação analgésica em estudos clínicos. Em vista disso, no presente estudo foram avaliadas as propriedades inibitórias sobre a atividade da MAO-A, assim como os potenciais antidepressivo e antinociceptivo do novo composto imidazolínico 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos. Foi observado que o 2-DMPI é um inibidor misto, reversível e preferencial da MAO-A. O tratamento com 2-DMPI (100-1000 μmol/kg, s.c.) produziu um efeito tipo-antidepressivo no teste de suspensão da cauda, sem afetar a atividade motora dos animais. Os camundongos tratados com 2-DMPI (300 μmol/kg, s.c.) apresentaram uma diminuição na taxa de renovação da serotonina e da dopamina em regiões cerebrais específicas, sugerindo que o efeito tipo-antidepressivo desse composto foi mediado pelos sistemas serotoninérgico e dopaminérgico. Isto foi confirmado por experimentos que mostraram que o efeito tipo-antidepressivo do 2-DMPI foi abolido pelo pré-tratamento com antagonistas de receptores serotoninérgicos e dopaminérgicos. A fim de avaliar um possível efeito antinociceptivo do 2-DMPI, foi utilizado um modelo de dor neuropática, induzida pela injúria por constrição crônica (CCI) do nervo ciático, em camundongos. Observou-se que os camundongos submetidos à CCI apresentaram um aumento na atividade da MAO-A na medula espinhal lombar comparado com os animais falso-operados e que o tratamento com 2-DMPI (30-300 μmol/kg, s.c.) reverteu a hiperalgesia mecânica induzida pela CCI. Além disso, o efeito antinociceptivo do 2-DMPI foi revertido pela administração intratecal do antagonista do receptor serotoninérgico 5-HT3, ondansetrona (10 μg/sítio). Esses resultados sugerem que o 2-DMPI, devido à sua capacidade de modular a atividade da MAO-A e, consequentemente, os sistemas monoaminérgicos, parece ser um protótipo promissor para o desenvolvimento de novos fármacos com propriedades antidepressiva e analgésica.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaDepressãoMetabolismo de monoaminasDor neuropáticaInibidor reversível da MAO-ADepressionMonoamine metabolismNeuropathic painReversible MAO-A inhibitorCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAPotencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongosAntidepressant and analgesic potential of 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisFerreira, Julianohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4768702Y6Rodrigues, Ana Lúcia Severohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785436H8Sauzem, Patricia Dutrahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4764634Z1Barreto, Katia Padilhahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4727510Z9Schetinger, Maria Rosa Chitolinahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4533353D6Villarinho, Jardel Gomes20100000000040030030030030030050000296dee-06fe-4bc6-a73d-5a0cdd89e3bcfd961a7a-e7a5-4d3b-b5a9-8a9c1cc0739a51038c1d-713d-4890-ac1c-4cdcedeba73bd902d780-cdc5-4148-8d1f-37d3722c5f6a4e7b5668-e7d0-477f-a5fa-5d2e2a47e3c698300743-ff68-46b6-b7c0-7145a94b913dinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALVILLARINHO, JARDEL GOMES.pdfapplication/pdf5942724http://repositorio.ufsm.br/bitstream/1/3835/1/VILLARINHO%2c%20JARDEL%20GOMES.pdfe5a0f0c1b5070b8266474a9e4ab2b669MD51TEXTVILLARINHO, JARDEL GOMES.pdf.txtVILLARINHO, JARDEL GOMES.pdf.txtExtracted texttext/plain137035http://repositorio.ufsm.br/bitstream/1/3835/2/VILLARINHO%2c%20JARDEL%20GOMES.pdf.txtcee43e544d3a2ee9ff6c80167cef1edaMD52THUMBNAILVILLARINHO, JARDEL GOMES.pdf.jpgVILLARINHO, JARDEL GOMES.pdf.jpgIM Thumbnailimage/jpeg5743http://repositorio.ufsm.br/bitstream/1/3835/3/VILLARINHO%2c%20JARDEL%20GOMES.pdf.jpgc13e4ee92bfcbfa3c7b14c9a0eacf88eMD531/38352022-03-07 16:36:23.761oai:repositorio.ufsm.br:1/3835Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132022-03-07T19:36:23Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
dc.title.alternative.eng.fl_str_mv |
Antidepressant and analgesic potential of 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice |
title |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
spellingShingle |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos Villarinho, Jardel Gomes Depressão Metabolismo de monoaminas Dor neuropática Inibidor reversível da MAO-A Depression Monoamine metabolism Neuropathic pain Reversible MAO-A inhibitor CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
title_full |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
title_fullStr |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
title_full_unstemmed |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
title_sort |
Potencial antidepressivo e analgésico do 2-(3,4-dimetoxi-fenil)-4,5-diidro-1H-imidazol (2-DMPI) em camundongos |
author |
Villarinho, Jardel Gomes |
author_facet |
Villarinho, Jardel Gomes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Ferreira, Juliano |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4768702Y6 |
dc.contributor.referee1.fl_str_mv |
Rodrigues, Ana Lúcia Severo |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785436H8 |
dc.contributor.referee2.fl_str_mv |
Sauzem, Patricia Dutra |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4764634Z1 |
dc.contributor.referee3.fl_str_mv |
Barreto, Katia Padilha |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4727510Z9 |
dc.contributor.referee4.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4533353D6 |
dc.contributor.author.fl_str_mv |
Villarinho, Jardel Gomes |
contributor_str_mv |
Ferreira, Juliano Rodrigues, Ana Lúcia Severo Sauzem, Patricia Dutra Barreto, Katia Padilha Schetinger, Maria Rosa Chitolina |
dc.subject.por.fl_str_mv |
Depressão Metabolismo de monoaminas Dor neuropática Inibidor reversível da MAO-A |
topic |
Depressão Metabolismo de monoaminas Dor neuropática Inibidor reversível da MAO-A Depression Monoamine metabolism Neuropathic pain Reversible MAO-A inhibitor CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Depression Monoamine metabolism Neuropathic pain Reversible MAO-A inhibitor |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Depression and chronic pain coexist in several patients and may be modulated by the same neurotransmitter systems. In this context, various studies have demonstrated that antidepressants from the class of the inhibitors of monoamine oxidase-A (MAO-A) enzyme presented antinociceptive effect in different pain models in experimental animals, as well as analgesic action in clinic studies. Thus, in the present study were evaluated the MAO-A inhibitory properties, as well as the antidepressant and antinociceptive potential of the novel imidazoline compound 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice. 2-DMPI showed to be a mixed, reversible and preferential MAO-A inhibitor. The treatment with 2-DMPI (100-1000 μmol/kg, s.c.) produced an antidepressant-like effect in the tail suspension test without affecting motor activity of the animals. The mice treated with 2-DMPI showed a decrease in serotonin and dopamine turnover in specific brain regions, suggesting that the antidepressant-like effect of this compound was mediated by serotonergic and dopaminergic systems. This was confirmed by experiments showing that the antidepressant-like effect of 2-DMPI was abolished by pretreatment with serotonergic and dopaminergic receptor antagonists. In order to evaluate a possible antinociceptive action of 2-DMPI, a mice model of neuropathic pain, induced by chronic constriction injury (CCI) of the sciatic nerve was used. It was observed that mice submitted to CCI presented an increase in MAO-A activity in lumbar spinal cord compared with sham-submitted mice and that the treatment with 2-DMPI (30-300 μmol/kg, s.c.) reversed the CCI-induced mechanical hyperalgesia. Furthermore, the antihyperalgesic effect of 2-DMPI was reversed by intrathecal injection of the serotonergic 5-HT3 receptor antagonist ondansetron (10 μg/site). These results suggest that 2-DMPI, due to its ability to modulate MAO-A activity and, consequently, the monoaminergic systems, could be a promising prototype to the development of new drugs with antidepressant and analgesic properties. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-12-18 |
dc.date.accessioned.fl_str_mv |
2013-08-22 |
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2013-08-22 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
VILLARINHO, Jardel Gomes. ANTIDEPRESSANT AND ANALGESIC POTENTIAL OF 2-(3,4-DIMETHOXY-PHENYL)-4,5-DIHYDRO-1H-IMIDAZOLE (2-DMPI) IN MICE. 2012. 92 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/3835 |
identifier_str_mv |
VILLARINHO, Jardel Gomes. ANTIDEPRESSANT AND ANALGESIC POTENTIAL OF 2-(3,4-DIMETHOXY-PHENYL)-4,5-DIHYDRO-1H-IMIDAZOLE (2-DMPI) IN MICE. 2012. 92 f. Tese (Doutorado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
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http://repositorio.ufsm.br/handle/1/3835 |
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por |
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por |
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201000000000 |
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Universidade Federal de Santa Maria |
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Programa de Pós-Graduação em Farmacologia |
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UFSM |
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Farmacologia |
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Universidade Federal de Santa Maria |
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