Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos
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: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/4401 |
Resumo: | Pain is a common symptom in clinical practice and many advances have been observed in order to obtain more effective analgesic molecules with fewer side effects. The present study evaluated the antinociceptive potential of four novel pyrazoles: 3-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF3), 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4), 3-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl3), and 4-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl4). The systemic administration of the compounds was effective for the inhibition of the nociception in chemical (formalin test, 0.03 -1.0 mmol/kg, i.p.) and thermal (hot-plate test, 0.1-1.0 mmol/kg, i.p.) models of pain. In addition, MPF4 also produced antinociception in models of inflammatory pain induced by Complete Freund s Adjuvant (CFA) or by incision procedure in paw of mice. The antinociceptive effect of MPF4 (1.0 mmol/kg, i.p.) was not reversed by yohimbine (0.15 mg/kg, i.p.) or p-chlorophenylalanine ethyl ester (PCPA; 300 mg/kg, i.p.), but by naloxone (2.0 mg/kg, i.p.), in both thermal and chemical nociception. Animals given MPF4 (1.0 mmol/kg, i.p.) daily for 8 days in a row, in contrast to morphine (5 mg/kg, i.p.), showed no tolerance to its antinociceptive effect or cross-tolerance with morphine. However, similarly to morphine (11 mg/kg, i.p.), MPF4 (1.0 mmol/kg, i.p.) reduced gastrointestinal transit in mice and its effect was reversed by naloxone (2.5 mg/kg, i.p.). Unlike indomethacin (0.1 mmol/kg, p.o.), MPF4 (1.0 mmol/kg, p.o.) did not induce gastric lesions in mice. The tested compounds did not impair locomotion in the mice as well. Taken together, the results demonstrate that these novel pyrazoline methyl esters evaluated may be promising prototypes of additional mild analgesics, which are therapeutically relevant. |
id |
UFSM_e99155cadd5e824d4ccafa88298143af |
---|---|
oai_identifier_str |
oai:repositorio.ufsm.br:1/4401 |
network_acronym_str |
UFSM |
network_name_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
repository_id_str |
|
spelling |
2017-04-242017-04-242008-07-11MILANO, Julie Maria. Evaluation of the antinociceptive effect of novel 5- trihalomethyl- 4,5- dihydro- 1h pyrazole methyl esteres in mice. 2008. 107 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008.http://repositorio.ufsm.br/handle/1/4401Pain is a common symptom in clinical practice and many advances have been observed in order to obtain more effective analgesic molecules with fewer side effects. The present study evaluated the antinociceptive potential of four novel pyrazoles: 3-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF3), 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4), 3-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl3), and 4-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl4). The systemic administration of the compounds was effective for the inhibition of the nociception in chemical (formalin test, 0.03 -1.0 mmol/kg, i.p.) and thermal (hot-plate test, 0.1-1.0 mmol/kg, i.p.) models of pain. In addition, MPF4 also produced antinociception in models of inflammatory pain induced by Complete Freund s Adjuvant (CFA) or by incision procedure in paw of mice. The antinociceptive effect of MPF4 (1.0 mmol/kg, i.p.) was not reversed by yohimbine (0.15 mg/kg, i.p.) or p-chlorophenylalanine ethyl ester (PCPA; 300 mg/kg, i.p.), but by naloxone (2.0 mg/kg, i.p.), in both thermal and chemical nociception. Animals given MPF4 (1.0 mmol/kg, i.p.) daily for 8 days in a row, in contrast to morphine (5 mg/kg, i.p.), showed no tolerance to its antinociceptive effect or cross-tolerance with morphine. However, similarly to morphine (11 mg/kg, i.p.), MPF4 (1.0 mmol/kg, i.p.) reduced gastrointestinal transit in mice and its effect was reversed by naloxone (2.5 mg/kg, i.p.). Unlike indomethacin (0.1 mmol/kg, p.o.), MPF4 (1.0 mmol/kg, p.o.) did not induce gastric lesions in mice. The tested compounds did not impair locomotion in the mice as well. Taken together, the results demonstrate that these novel pyrazoline methyl esters evaluated may be promising prototypes of additional mild analgesics, which are therapeutically relevant.A dor é um sintoma comum na prática clínica, por isso muitos avanços estão sendo realizados no sentido de obter moléculas analgésicas cada vez mais efetivas e com menos efeitos colaterais. Neste contexto, no presente estudo avaliou-se o potencial antinociceptivo de quatro pirazóis inéditos: 3- metil-5-hidroxi-5-trifluormetil-4,5-diidro- 1H-pirazol metil éster (MPF3), 4-metil-5-hidroxi-5-trifluormetil-4,5-diidro-1H-pirazol metil éster (MPF4), 3-metil-5-hidroxi-5-triclorometil-4,5-diidro-1H-pirazol metil éster (MPCl3) e 4-metil-5-hidroxi-5-triclorometil-4,5-diidro-1H-pirazol metil éster (MPCl4). A administração sistêmica dos compostos foi efetiva em inibir a nocicepção em modelos de dor induzida por estímulo nocivo químico (teste da formalina, 0,03-1,0 mmol/kg, i.p.) e térmico (teste da placa-quente, 0,1-1,0 mmol/kg, i.p.). Em adição, MPF4 produziu antinocicepção em modelos de dor inflamatória causada por Adjuvante Completo de Freund (ACF) ou por incisão na pata de camundongos. O efeito antinociceptivo de MPF4 (1,0 mmol/kg, i.p.) não foi revertido pelo prétratamento dos animais com ioimbina (0,15 mg/kg, i.p.) ou p-clorofenilalanina etil éster (PCPA; 300 mg/kg, i.p.), mas sim, por naloxona (2,0 mg/kg, i.p.), tanto na nocicepção térmica quanto na nocicepção química. O tratamento dos animais durante um período de 8 dias consecutivos com MPF4 (1,0 mmol/kg, i.p), ao contrário daqueles tratados com morfina (5,0 mg/kg, i.p.), não desenvolveram tolerância antinociceptiva nem tolerância cruzada com os animais tolerantes à morfina. Porém, similar ao opióide morfina (11 mg/kg, i.p.), MPF4 (1,0 mmol/kg, i.p) inibiu o trânsito gastrintestinal de camundongos, sendo este efeito revertido por naloxona (2,5 mg/kg, i.p.). Além disso, diferente de indometacina (0,1 mmol/kg, v.o.), MPF4 (1,0 mmol/kg, v.o.) não induziu lesão gástrica em camundongos. Nenhum dos compostos testados causou alteração na atividade locomotora dos camundongos. Estes achados sugerem que os novos pirazoline metil ésteres avaliados parecem ser promissores para o desenvolvimento de novas drogas analgésicas terapeuticamente relevantes.application/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaAntinocicepçãoPirazoline metil éstersDorAnalgésicosAntinociceptionPyrazoline methyl esteresPainAnalgesicsCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAvaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongosEvaluation of the antinociceptive effect of novel 5- trihalomethyl- 4,5- dihydro- 1h pyrazole methyl esteres in miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBonacorso, Helio Gauzehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788537E0Rubin, Maribel Antonellohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7Dalmaz, Carlahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4787286Z1Schetinger, Maria Rosa ChitolinaZanatta, Nilohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783100P9Emanuelli, Tatianahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797080Z5http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4775576Y3Milano, Julie Maria20080000000240050030030030050050050006c852ad-d805-43c3-99d6-93a6a86f507c4ba83e85-e7a4-49a9-858d-bc54e016cb1f74f338b3-c49d-4361-af88-6c6fde546084b5bee2d7-1e05-4f4b-bbc2-2e60b8cfb4ec93acb9e6-39fa-412c-84a4-a90a4863b53ea3caf96b-54e9-4f59-95af-1941d0bb008722aa7bd2-5905-49f4-b5ac-e7167850124finfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALJULIEMARIAMILANO.pdfapplication/pdf1475336http://repositorio.ufsm.br/bitstream/1/4401/1/JULIEMARIAMILANO.pdf0528614a45b2340c9b2c77e61a56aa0cMD51TEXTJULIEMARIAMILANO.pdf.txtJULIEMARIAMILANO.pdf.txtExtracted texttext/plain217878http://repositorio.ufsm.br/bitstream/1/4401/2/JULIEMARIAMILANO.pdf.txtb295e65a055bd62fefcb192ddf0cf27eMD52THUMBNAILJULIEMARIAMILANO.pdf.jpgJULIEMARIAMILANO.pdf.jpgIM Thumbnailimage/jpeg5939http://repositorio.ufsm.br/bitstream/1/4401/3/JULIEMARIAMILANO.pdf.jpgebaa4e087d569f1bf78cca17f634c0e3MD531/44012017-07-25 11:06:37.117oai:repositorio.ufsm.br:1/4401Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-07-25T14:06:37Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
dc.title.alternative.eng.fl_str_mv |
Evaluation of the antinociceptive effect of novel 5- trihalomethyl- 4,5- dihydro- 1h pyrazole methyl esteres in mice |
title |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
spellingShingle |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos Milano, Julie Maria Antinocicepção Pirazoline metil ésters Dor Analgésicos Antinociception Pyrazoline methyl esteres Pain Analgesics CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
title_full |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
title_fullStr |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
title_full_unstemmed |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
title_sort |
Avaliação do potencial antinociceptivo de 5- trialometil- 4,5-diidro-1h- pirazol metil ésteres inéditos em camundongos |
author |
Milano, Julie Maria |
author_facet |
Milano, Julie Maria |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bonacorso, Helio Gauze |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788537E0 |
dc.contributor.advisor-co1.fl_str_mv |
Rubin, Maribel Antonello |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4794806H7 |
dc.contributor.referee1.fl_str_mv |
Dalmaz, Carla |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4787286Z1 |
dc.contributor.referee2.fl_str_mv |
Schetinger, Maria Rosa Chitolina |
dc.contributor.referee3.fl_str_mv |
Zanatta, Nilo |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4783100P9 |
dc.contributor.referee4.fl_str_mv |
Emanuelli, Tatiana |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4797080Z5 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4775576Y3 |
dc.contributor.author.fl_str_mv |
Milano, Julie Maria |
contributor_str_mv |
Bonacorso, Helio Gauze Rubin, Maribel Antonello Dalmaz, Carla Schetinger, Maria Rosa Chitolina Zanatta, Nilo Emanuelli, Tatiana |
dc.subject.por.fl_str_mv |
Antinocicepção Pirazoline metil ésters Dor Analgésicos |
topic |
Antinocicepção Pirazoline metil ésters Dor Analgésicos Antinociception Pyrazoline methyl esteres Pain Analgesics CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Antinociception Pyrazoline methyl esteres Pain Analgesics |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Pain is a common symptom in clinical practice and many advances have been observed in order to obtain more effective analgesic molecules with fewer side effects. The present study evaluated the antinociceptive potential of four novel pyrazoles: 3-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF3), 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4), 3-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl3), and 4-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPCl4). The systemic administration of the compounds was effective for the inhibition of the nociception in chemical (formalin test, 0.03 -1.0 mmol/kg, i.p.) and thermal (hot-plate test, 0.1-1.0 mmol/kg, i.p.) models of pain. In addition, MPF4 also produced antinociception in models of inflammatory pain induced by Complete Freund s Adjuvant (CFA) or by incision procedure in paw of mice. The antinociceptive effect of MPF4 (1.0 mmol/kg, i.p.) was not reversed by yohimbine (0.15 mg/kg, i.p.) or p-chlorophenylalanine ethyl ester (PCPA; 300 mg/kg, i.p.), but by naloxone (2.0 mg/kg, i.p.), in both thermal and chemical nociception. Animals given MPF4 (1.0 mmol/kg, i.p.) daily for 8 days in a row, in contrast to morphine (5 mg/kg, i.p.), showed no tolerance to its antinociceptive effect or cross-tolerance with morphine. However, similarly to morphine (11 mg/kg, i.p.), MPF4 (1.0 mmol/kg, i.p.) reduced gastrointestinal transit in mice and its effect was reversed by naloxone (2.5 mg/kg, i.p.). Unlike indomethacin (0.1 mmol/kg, p.o.), MPF4 (1.0 mmol/kg, p.o.) did not induce gastric lesions in mice. The tested compounds did not impair locomotion in the mice as well. Taken together, the results demonstrate that these novel pyrazoline methyl esters evaluated may be promising prototypes of additional mild analgesics, which are therapeutically relevant. |
publishDate |
2008 |
dc.date.issued.fl_str_mv |
2008-07-11 |
dc.date.accessioned.fl_str_mv |
2017-04-24 |
dc.date.available.fl_str_mv |
2017-04-24 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MILANO, Julie Maria. Evaluation of the antinociceptive effect of novel 5- trihalomethyl- 4,5- dihydro- 1h pyrazole methyl esteres in mice. 2008. 107 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4401 |
identifier_str_mv |
MILANO, Julie Maria. Evaluation of the antinociceptive effect of novel 5- trihalomethyl- 4,5- dihydro- 1h pyrazole methyl esteres in mice. 2008. 107 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2008. |
url |
http://repositorio.ufsm.br/handle/1/4401 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
400 500 300 300 300 500 500 500 |
dc.relation.authority.fl_str_mv |
06c852ad-d805-43c3-99d6-93a6a86f507c 4ba83e85-e7a4-49a9-858d-bc54e016cb1f 74f338b3-c49d-4361-af88-6c6fde546084 b5bee2d7-1e05-4f4b-bbc2-2e60b8cfb4ec 93acb9e6-39fa-412c-84a4-a90a4863b53e a3caf96b-54e9-4f59-95af-1941d0bb0087 22aa7bd2-5905-49f4-b5ac-e7167850124f |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/4401/1/JULIEMARIAMILANO.pdf http://repositorio.ufsm.br/bitstream/1/4401/2/JULIEMARIAMILANO.pdf.txt http://repositorio.ufsm.br/bitstream/1/4401/3/JULIEMARIAMILANO.pdf.jpg |
bitstream.checksum.fl_str_mv |
0528614a45b2340c9b2c77e61a56aa0c b295e65a055bd62fefcb192ddf0cf27e ebaa4e087d569f1bf78cca17f634c0e3 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1793240121555812352 |