Traxoprodil atenua as convulsões induzidas por pentilenotetrazol
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/8951 |
Resumo: | There is evidence that while polyamines facilitate seizures by positively modulating N-methyl-D-aspartate receptors (NMDAr), selective antagonists of the NR2B-subunit decrease seizures. However, it remains undetermined whether traxoprodil (CP-101,606), an ifenprodil analog that acts as a selective antagonist of the NR2B subunit of the NMDAr, decreases seizure activity. In the current study we investigated whether traxoprodil alters PTZ-induced seizures in adult male Wistar rats by behavioral and electroencephalographical methods. Spermidine (SPD) (2 nmol/site; i.c.v.) facilitated behavioral and electroencephalographical seizures induced by a normally subeffective dose of PTZ (35 mg/kg; i.p.), but did not alter seizure activity induced by convulsant dose of PTZ (70 mg/kg; i.p). Traxoprodil (20 nmol i.c.v.) increased the latency to generalized tonic clonic seizures induced by PTZ (70 mg/kg; i.p). The oral administration of traxoprodil (60 mg/kg) increased the latency to clonic and tonic-clonic seizures, and decreased total time spent in seizures. These data constitute pharmacological evidence supporting a role for NR2B subunit in PTZ-induced seizures. While more studies are necessary to determine whether traxoprodil is a useful anticonvulsant in clinical settings, NR2B subunits may represent new targets of drug development for convulsive disorders. |
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Traxoprodil atenua as convulsões induzidas por pentilenotetrazolTraxoprodil attenuates pentylenetetrazol-induced seizuresTraxoprodilNR2BCP-101,606PoliaminasEspermidinaConvulsõesPTZPolyaminesSpermidineSeizuresCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAThere is evidence that while polyamines facilitate seizures by positively modulating N-methyl-D-aspartate receptors (NMDAr), selective antagonists of the NR2B-subunit decrease seizures. However, it remains undetermined whether traxoprodil (CP-101,606), an ifenprodil analog that acts as a selective antagonist of the NR2B subunit of the NMDAr, decreases seizure activity. In the current study we investigated whether traxoprodil alters PTZ-induced seizures in adult male Wistar rats by behavioral and electroencephalographical methods. Spermidine (SPD) (2 nmol/site; i.c.v.) facilitated behavioral and electroencephalographical seizures induced by a normally subeffective dose of PTZ (35 mg/kg; i.p.), but did not alter seizure activity induced by convulsant dose of PTZ (70 mg/kg; i.p). Traxoprodil (20 nmol i.c.v.) increased the latency to generalized tonic clonic seizures induced by PTZ (70 mg/kg; i.p). The oral administration of traxoprodil (60 mg/kg) increased the latency to clonic and tonic-clonic seizures, and decreased total time spent in seizures. These data constitute pharmacological evidence supporting a role for NR2B subunit in PTZ-induced seizures. While more studies are necessary to determine whether traxoprodil is a useful anticonvulsant in clinical settings, NR2B subunits may represent new targets of drug development for convulsive disorders.Há evidências de que as poliaminas facilitam convulsões por modular positivamente os receptores N-metil-D-aspartato (NMDAr), e que os antagonistas seletivos a subunidade NR2B do NMDAr têm atividade anticonvulsivante. Entretanto, permanece indeterminado se o traxoprodil (CP-101,606), um análogo do ifenprodil que age como antagonista seletivo na subunidade NR2B do NMDAr, tem efeito anticonvulsivante. Neste estudo investigamos se o traxoprodil altera as convulsões induzidas por pentilenotetrazol (PTZ) em ratos Wistar machos por meio de métodos comportamentais e eletroencéfalográficos (EEG). Espermidina (SPD) (2 nmol/sítio; i.c.v.) facilita as convulsões comportamentais e eletroencéfalográficas induzidas por doses subconvulsivantes de PTZ (35 mg/kg; i.p.), mas não altera a atividade convulsiva induzida por dose plenamente convulsivante de PTZ (70 mg/kg; i.p.). Traxoprodil (20 nmol i.c.v.) aumenta a latência para convulsão tônico-clônica generalizada induzida por PTZ (70 mg/kg; i.p.). A administração oral de traxoprodil (60 mg/kg) aumenta as latências para convulsão clônica e tônico-clônica generalizada e diminui a duração total das convulsões induzidas por PTZ (70 mg/kg; i.p.). Esses dados mostram que o traxoprodil diminui as convulsões induzidas por PTZ, um modelo animal com bom poder de predição de atividade convulsivante em humanos, e sugerem um papel para a subunidade NR2B nas convulsões induzidas por PTZ. Enquanto mais estudos são necessários para determinar se o traxoprodil tem, de fato, atividade anticonvulsivante na clínica, as subunidades NR2B podem representar um novo alvo para o desenvolvimento de drogas anticonvulsivantes.Universidade Federal de Santa MariaBRFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaMello, Carlos Fernando dehttp://lattes.cnpq.br/3913887223894236Cysneiros, Roberta Monterazzohttp://lattes.cnpq.br/9822955080635086Fighera, Michele Rechiahttp://lattes.cnpq.br/8583392747509231Martignoni, Felipe Villa2011-01-312011-01-312010-09-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfMARTIGNONI, Felipe Villa. Traxoprodil attenuates pentylenetetrazol-induced seizures. 2010. 88 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010.http://repositorio.ufsm.br/handle/1/8951porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-01-07T11:06:38Zoai:repositorio.ufsm.br:1/8951Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-01-07T11:06:38Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol Traxoprodil attenuates pentylenetetrazol-induced seizures |
title |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol |
spellingShingle |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol Martignoni, Felipe Villa Traxoprodil NR2B CP-101,606 Poliaminas Espermidina Convulsões PTZ Polyamines Spermidine Seizures CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol |
title_full |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol |
title_fullStr |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol |
title_full_unstemmed |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol |
title_sort |
Traxoprodil atenua as convulsões induzidas por pentilenotetrazol |
author |
Martignoni, Felipe Villa |
author_facet |
Martignoni, Felipe Villa |
author_role |
author |
dc.contributor.none.fl_str_mv |
Mello, Carlos Fernando de http://lattes.cnpq.br/3913887223894236 Cysneiros, Roberta Monterazzo http://lattes.cnpq.br/9822955080635086 Fighera, Michele Rechia http://lattes.cnpq.br/8583392747509231 |
dc.contributor.author.fl_str_mv |
Martignoni, Felipe Villa |
dc.subject.por.fl_str_mv |
Traxoprodil NR2B CP-101,606 Poliaminas Espermidina Convulsões PTZ Polyamines Spermidine Seizures CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Traxoprodil NR2B CP-101,606 Poliaminas Espermidina Convulsões PTZ Polyamines Spermidine Seizures CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
There is evidence that while polyamines facilitate seizures by positively modulating N-methyl-D-aspartate receptors (NMDAr), selective antagonists of the NR2B-subunit decrease seizures. However, it remains undetermined whether traxoprodil (CP-101,606), an ifenprodil analog that acts as a selective antagonist of the NR2B subunit of the NMDAr, decreases seizure activity. In the current study we investigated whether traxoprodil alters PTZ-induced seizures in adult male Wistar rats by behavioral and electroencephalographical methods. Spermidine (SPD) (2 nmol/site; i.c.v.) facilitated behavioral and electroencephalographical seizures induced by a normally subeffective dose of PTZ (35 mg/kg; i.p.), but did not alter seizure activity induced by convulsant dose of PTZ (70 mg/kg; i.p). Traxoprodil (20 nmol i.c.v.) increased the latency to generalized tonic clonic seizures induced by PTZ (70 mg/kg; i.p). The oral administration of traxoprodil (60 mg/kg) increased the latency to clonic and tonic-clonic seizures, and decreased total time spent in seizures. These data constitute pharmacological evidence supporting a role for NR2B subunit in PTZ-induced seizures. While more studies are necessary to determine whether traxoprodil is a useful anticonvulsant in clinical settings, NR2B subunits may represent new targets of drug development for convulsive disorders. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-09-23 2011-01-31 2011-01-31 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
MARTIGNONI, Felipe Villa. Traxoprodil attenuates pentylenetetrazol-induced seizures. 2010. 88 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010. http://repositorio.ufsm.br/handle/1/8951 |
identifier_str_mv |
MARTIGNONI, Felipe Villa. Traxoprodil attenuates pentylenetetrazol-induced seizures. 2010. 88 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2010. |
url |
http://repositorio.ufsm.br/handle/1/8951 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Farmacologia UFSM Programa de Pós-Graduação em Farmacologia |
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reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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Universidade Federal de Santa Maria (UFSM) |
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UFSM |
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UFSM |
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Manancial - Repositório Digital da UFSM |
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Manancial - Repositório Digital da UFSM |
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Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
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atendimento.sib@ufsm.br||tedebc@gmail.com |
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