Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica
Ano de defesa: | 2008 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
BR
|
Palavras-chave em Português: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/4404 |
Resumo: | To identify the origin of pain and relieve of it is, certainly, important part of the treatment of any pathology. Unfortunately, nor all pain modalities possess an adequate treatment at a moment. Many patients do not obtain pain relief in response to drugs available or, they present serious adverse effects that hinder the continuity of treatment. So, a search for new drugs that are more efficient and that produce little undesired effect is necessary. Pyrazole derivatives are known for their excellent effectiveness as analgesics. In this context, the NUQUIMHE and LABNEURO have joined efforts for synthesize and evaluate the biological effects of several pyrazole compounds. In the present study, was evaluated the antinociceptive and antiedematogenic effect of one series of 5-trifluoromethyl-4,5-dihidro-1H-pyrazole-1- carboxiamide (2a-j) derivatives on acute and chronic nociception models in mice and rats. A preliminary evaluation of the toxicity for more active compounds, after their chronic administration, was carried out too. Some biochemistry parameters relationships to inflammation were also evaluated. Eight of ten compounds analyzed present antinociceptive effect on formalin test in mice. The two most efficient derivatives (2c and 2j) were also evaluated on hot plate, carrageenan and arthritis induced by Complete Freund Adjuvant (CFA). These compounds caused no effect against thermal nociception, but were effective for decrease the edema carrageenaninduced in mice. In the arthritis model in rats, 2c and 2j compounds caused antinociception, but do not antiedematogenic action. This antinociceptive effect occurred after acute and chronic administration and has long duration. Parameters indicators of liver and kidney lesion (urea, creatinine, aspartate aminotransferase and alanine aminotransferase) were not altered and were neither detected signals of gastric mucosa lesion nor evidences of tolerance development to antinociceptive effect in rats chronically treated with 2c or 2j. The serum level of haptoglobin and the tissue myeloperoxidase activity of the animals that received treatment indicate that these compounds did not present anti-inflammatory effect. None compounds evaluated caused alteration on locomotors activity of mice and rats. The results obtained in the present work suggest that this new class of pyrazole derivatives seems promising for development of new analgesic drugs. |
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2017-04-262017-04-262008-08-06SAUZEM, Patricia Dutra. Antinociceptive activity of 5-trifluoromethyil-4,5-dihidro-1hpyrazole-1-carboxiamide derivatives in animal models of acute and chronic nociception. 2008. 163 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008.http://repositorio.ufsm.br/handle/1/4404To identify the origin of pain and relieve of it is, certainly, important part of the treatment of any pathology. Unfortunately, nor all pain modalities possess an adequate treatment at a moment. Many patients do not obtain pain relief in response to drugs available or, they present serious adverse effects that hinder the continuity of treatment. So, a search for new drugs that are more efficient and that produce little undesired effect is necessary. Pyrazole derivatives are known for their excellent effectiveness as analgesics. In this context, the NUQUIMHE and LABNEURO have joined efforts for synthesize and evaluate the biological effects of several pyrazole compounds. In the present study, was evaluated the antinociceptive and antiedematogenic effect of one series of 5-trifluoromethyl-4,5-dihidro-1H-pyrazole-1- carboxiamide (2a-j) derivatives on acute and chronic nociception models in mice and rats. A preliminary evaluation of the toxicity for more active compounds, after their chronic administration, was carried out too. Some biochemistry parameters relationships to inflammation were also evaluated. Eight of ten compounds analyzed present antinociceptive effect on formalin test in mice. The two most efficient derivatives (2c and 2j) were also evaluated on hot plate, carrageenan and arthritis induced by Complete Freund Adjuvant (CFA). These compounds caused no effect against thermal nociception, but were effective for decrease the edema carrageenaninduced in mice. In the arthritis model in rats, 2c and 2j compounds caused antinociception, but do not antiedematogenic action. This antinociceptive effect occurred after acute and chronic administration and has long duration. Parameters indicators of liver and kidney lesion (urea, creatinine, aspartate aminotransferase and alanine aminotransferase) were not altered and were neither detected signals of gastric mucosa lesion nor evidences of tolerance development to antinociceptive effect in rats chronically treated with 2c or 2j. The serum level of haptoglobin and the tissue myeloperoxidase activity of the animals that received treatment indicate that these compounds did not present anti-inflammatory effect. None compounds evaluated caused alteration on locomotors activity of mice and rats. The results obtained in the present work suggest that this new class of pyrazole derivatives seems promising for development of new analgesic drugs.Identificar a causa da dor e aliviá-la é, com certeza, parte importante do tratamento de qualquer patologia. Infelizmente, nem todas as modalidades de dor possuem um tratamento adequado atualmente. Muitos pacientes não respondem aos fármacos disponíveis ou, então apresentam efeitos adversos graves que impedem a continuidade do tratamento. Desta forma, existe a necessidade de pesquisar novas drogas que sejam mais eficazes e que produzam menos efeitos indesejados. Os derivados pirazolínicos são conhecidos pela sua excelente eficácia como analgésicos. Por esse motivo, o NUQUIMHE e o LABNEURO têm unido esforços na intenção de sintetizar e avaliar os efeitos biológicos de vários compostos pirazolínicos. No presente trabalho, foi avaliado o efeito antinociceptivo e antiedematogênico de uma série de derivados 5-trifluormetil-4,5-diidro-1H-pirazol carboxiamida (2a-j) em modelos de nocicepção aguda e crônica em camundongos e ratos. Também foi feita uma avaliação preliminar da toxicidade dos compostos mais ativos, após administração crônica, além da avaliação de alguns parâmetros bioquímicos relacionados à inflamação. Oito dos 10 compostos testados apresentaram efeito antinociceptivo no teste da formalina em camundongos. Os dois compostos de maior eficácia (2c e 2j) foram também avaliados nos testes da placa quente, da carragenina e da artrite induzida por adjuvante completo de Freund (CFA). Tais compostos não causaram efeito na nocicepção térmica, mas foram eficazes na diminuição do edema induzido por carragenina em camundongos. No modelo de artrite em ratos, os compostos 2c e 2j causaram antinocicepção, mas não diminuição do edema. Esse efeito foi observado após administração aguda e crônica, e teve longa duração. Os níveis séricos de haptoglobina e a atividade tecidual da mieloperoxidase não se apresentaram alterados nos ratos tratados cronicamente com 2c e 2j, indicando que esses compostos, provavelmente, não possuem ação antiinflamatória. Os parâmetros de toxicidade renal e hepática (uréia, creatinina, aspartato aminotransferase e alanina aminotrasferase) não se apresentaram alterados, bem como não foram encontrados sinais de lesão da mucosa gástrica, nem evidências de desenvolvimento de tolerância ao efeito antinociceptivo nos ratos tratados cronicamente com 2c e 2j. Nenhum dos compostos testados causou alteração na atividade locomotora de camundongos e ratos. Os resultados encontrados neste trabalho sugerem que essa nova classe de derivados pirazolínicos parece promissora no que diz respeito ao desenvolvimento de novas drogas analgésicas.application/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaAntinocicepçãoPirazolínicosFarmacologia da dorCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAtividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônicaAntinociceptive activity of 5-trifluoromethyil-4,5-dihidro-1hpyrazole-1-carboxiamide derivatives in animal models of acute and chronic nociceptioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRubin, Maribel Antonellohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7Ferreira, Julianohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4768702Y6Flores, Alex Fabiani Clarohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782774Y0Assreuy, Jamilhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4721449Z1Pereira, Maria Esterhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728086Y2Schetinger, Maria Rosa Chitolinahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4764634Z1Sauzem, Patricia Dutra20080000000240030030030050030030050017f72a93-232f-40b3-9c14-1b54b978789b8094411c-c0bb-4b7e-a2b3-aa07422baff86aa4fb21-f237-4f22-91a2-3a4524e0772f4d308e51-3866-4274-9e77-03644c9383dfd06c3502-d900-4c98-b960-a703dd00a6fb8715a925-41b6-4b21-bdcf-a45ad2f0af9a98300743-ff68-46b6-b7c0-7145a94b913dinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALPATRCIADUTRASAUZEM.pdfapplication/pdf4566924http://repositorio.ufsm.br/bitstream/1/4404/1/PATRCIADUTRASAUZEM.pdf38c16c775f1230c64c56ef9c329052f9MD51TEXTPATRCIADUTRASAUZEM.pdf.txtPATRCIADUTRASAUZEM.pdf.txtExtracted texttext/plain246422http://repositorio.ufsm.br/bitstream/1/4404/2/PATRCIADUTRASAUZEM.pdf.txt63ff9406056ff382f70cdc98c766e1b5MD52THUMBNAILPATRCIADUTRASAUZEM.pdf.jpgPATRCIADUTRASAUZEM.pdf.jpgIM Thumbnailimage/jpeg5758http://repositorio.ufsm.br/bitstream/1/4404/3/PATRCIADUTRASAUZEM.pdf.jpgc1e2551b9ade41080a56e55472a7da4fMD531/44042017-07-25 11:06:34.148oai:repositorio.ufsm.br:1/4404Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132017-07-25T14:06:34Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
dc.title.alternative.eng.fl_str_mv |
Antinociceptive activity of 5-trifluoromethyil-4,5-dihidro-1hpyrazole-1-carboxiamide derivatives in animal models of acute and chronic nociception |
title |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
spellingShingle |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica Sauzem, Patricia Dutra Antinocicepção Pirazolínicos Farmacologia da dor CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
title_full |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
title_fullStr |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
title_full_unstemmed |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
title_sort |
Atividade antinociceptiva de derivados 5-trifluormetil-4,5-diidro-1h-pirazol-1-carboxiamida em modelos animais de nocicepção aguda e crônica |
author |
Sauzem, Patricia Dutra |
author_facet |
Sauzem, Patricia Dutra |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rubin, Maribel Antonello |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7 |
dc.contributor.advisor-co1.fl_str_mv |
Ferreira, Juliano |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4768702Y6 |
dc.contributor.referee1.fl_str_mv |
Flores, Alex Fabiani Claro |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782774Y0 |
dc.contributor.referee2.fl_str_mv |
Assreuy, Jamil |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4721449Z1 |
dc.contributor.referee3.fl_str_mv |
Pereira, Maria Ester |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728086Y2 |
dc.contributor.referee4.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4764634Z1 |
dc.contributor.author.fl_str_mv |
Sauzem, Patricia Dutra |
contributor_str_mv |
Rubin, Maribel Antonello Ferreira, Juliano Flores, Alex Fabiani Claro Assreuy, Jamil Pereira, Maria Ester Schetinger, Maria Rosa Chitolina |
dc.subject.por.fl_str_mv |
Antinocicepção Pirazolínicos Farmacologia da dor |
topic |
Antinocicepção Pirazolínicos Farmacologia da dor CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
To identify the origin of pain and relieve of it is, certainly, important part of the treatment of any pathology. Unfortunately, nor all pain modalities possess an adequate treatment at a moment. Many patients do not obtain pain relief in response to drugs available or, they present serious adverse effects that hinder the continuity of treatment. So, a search for new drugs that are more efficient and that produce little undesired effect is necessary. Pyrazole derivatives are known for their excellent effectiveness as analgesics. In this context, the NUQUIMHE and LABNEURO have joined efforts for synthesize and evaluate the biological effects of several pyrazole compounds. In the present study, was evaluated the antinociceptive and antiedematogenic effect of one series of 5-trifluoromethyl-4,5-dihidro-1H-pyrazole-1- carboxiamide (2a-j) derivatives on acute and chronic nociception models in mice and rats. A preliminary evaluation of the toxicity for more active compounds, after their chronic administration, was carried out too. Some biochemistry parameters relationships to inflammation were also evaluated. Eight of ten compounds analyzed present antinociceptive effect on formalin test in mice. The two most efficient derivatives (2c and 2j) were also evaluated on hot plate, carrageenan and arthritis induced by Complete Freund Adjuvant (CFA). These compounds caused no effect against thermal nociception, but were effective for decrease the edema carrageenaninduced in mice. In the arthritis model in rats, 2c and 2j compounds caused antinociception, but do not antiedematogenic action. This antinociceptive effect occurred after acute and chronic administration and has long duration. Parameters indicators of liver and kidney lesion (urea, creatinine, aspartate aminotransferase and alanine aminotransferase) were not altered and were neither detected signals of gastric mucosa lesion nor evidences of tolerance development to antinociceptive effect in rats chronically treated with 2c or 2j. The serum level of haptoglobin and the tissue myeloperoxidase activity of the animals that received treatment indicate that these compounds did not present anti-inflammatory effect. None compounds evaluated caused alteration on locomotors activity of mice and rats. The results obtained in the present work suggest that this new class of pyrazole derivatives seems promising for development of new analgesic drugs. |
publishDate |
2008 |
dc.date.issued.fl_str_mv |
2008-08-06 |
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2017-04-26 |
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2017-04-26 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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dc.identifier.citation.fl_str_mv |
SAUZEM, Patricia Dutra. Antinociceptive activity of 5-trifluoromethyil-4,5-dihidro-1hpyrazole-1-carboxiamide derivatives in animal models of acute and chronic nociception. 2008. 163 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4404 |
identifier_str_mv |
SAUZEM, Patricia Dutra. Antinociceptive activity of 5-trifluoromethyil-4,5-dihidro-1hpyrazole-1-carboxiamide derivatives in animal models of acute and chronic nociception. 2008. 163 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008. |
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http://repositorio.ufsm.br/handle/1/4404 |
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