Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/59406
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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampToque, Haroldo Alfredo Florespt_BR
dc.contributor.authorunicampDe Nucci, Gilbertopt_BR
dc.contributor.authorunicampAntunes, Edsonpt_BR
dc.typeArtigopt_BR
dc.titlePharmacological characterization of a novel phosphodiesterase type 5 (PDE5) inhibitor lodenafil carbonate on human and rabbit corpus cavernosumpt_BR
dc.contributor.authorToque, H.A.pt_BR
dc.contributor.authorDe Nucci, G.pt_BR
dc.contributor.authorTeixeira, C.E.pt_BR
dc.contributor.authorLorenzetti, R.pt_BR
dc.contributor.authorOkuyama, C.E.pt_BR
dc.contributor.authorAntunes, E.pt_BR
dc.subjectGMP cíclicopt_BR
dc.subjectDisfunção erétilpt_BR
dc.subjectCitrato de sildenafilapt_BR
dc.subjectÓxido nítricopt_BR
dc.subject.otherlanguageErectile dysfunctionpt_BR
dc.subject.otherlanguageSildenafil citratept_BR
dc.subject.otherlanguageNitric oxidept_BR
dc.subject.otherlanguageCyclic GMPpt_BR
dc.description.abstractNitrergic nerves and endothelial cells release nitric oxide (NO) in the corpus cavernosum, a key mediator that stimulates soluble guanylyl cyclase to increase cGMP levels causing penile erection. Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong the NO effects by inhibiting cGMP breakdown. Here, we report a novel PDE5 inhibitor, lodenafil carbonate, (Bis-(2-(4-[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-benzenesulfonyl]piperazin-1-yl)-ethyl)carbonate) that is a dimer of lodenafil. We therefore aimed to compare the effects of sildenafil, lodenafil and lodenafil carbonate on in vitro human and rabbit cavernosal relaxations, activity of crude PDE extracts from human platelets, as well as stability and metabolic studies in rat, dog and human plasma. Pharmacokinetic evaluations after intravenous and oral administration were performed in male beagles. Functional experiments were conducted using organ bath techniques. Pharmacokinetics was studied in beagles by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), following oral or intravascular administration. All PDE5 inhibitors tested concentration-dependently relaxed (0.001-100 mu M) phenylephrine-precontracted rabbit and human corpus cavernosum. The cavernosal relaxations evoked by either acetylcholine (0.01-100 mu M) or electrical field stimulation (EFS, 1-20 Hz) were markedly potentiated by sildenafil, lodenafil and lodenafil carbonate. Lodenafil carbonate was more potent to inhibit the cGMP hydrolysis in POE extracts compared with lodenafil and sildenafil. Following intravascular and single oral administration of lodenafil carbonate, only lodenafil and norlodenafil were detected in vivo. These results indicate that lodenafil carbonate works as a prodrug, being lodenafil the active moiety of lodenafil carbonatept
dc.relation.ispartofEuropean journal of pharmacologypt_BR
dc.relation.ispartofabbreviationEur. j. pharmacol.pt_BR
dc.publisher.cityAmsterdam pt_BR
dc.publisher.countryPaíses Baixospt_BR
dc.publisherElsevierpt_BR
dc.date.issued2008pt_BR
dc.date.monthofcirculationSept.pt_BR
dc.language.isoengpt_BR
dc.description.volume591pt_BR
dc.description.issuenumber1-3pt_BR
dc.description.firstpage189pt_BR
dc.description.lastpage195pt_BR
dc.rightsFechadopt_BR
dc.sourceWOSpt_BR
dc.identifier.issn0014-2999pt_BR
dc.identifier.eissn1879-0712pt_BR
dc.identifier.doi10.1016/j.ejphar.2008.06.055pt_BR
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0014299908006699pt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPpt_BR
dc.description.sponsordocumentnumbersem informaçãopt_BR
dc.date.available2014-11-16T10:14:55Z-
dc.date.available2015-11-26T16:21:52Z-
dc.date.accessioned2014-11-16T10:14:55Z-
dc.date.accessioned2015-11-26T16:21:52Z-
dc.description.provenanceMade available in DSpace on 2014-11-16T10:14:55Z (GMT). No. of bitstreams: 1 WOS000259162300030.pdf: 730438 bytes, checksum: 6fd6586818032dddd328684b52226ce7 (MD5) Previous issue date: 2008en
dc.description.provenanceMade available in DSpace on 2015-11-26T16:21:52Z (GMT). No. of bitstreams: 2 WOS000259162300030.pdf: 730438 bytes, checksum: 6fd6586818032dddd328684b52226ce7 (MD5) WOS000259162300030.pdf.txt: 39364 bytes, checksum: 823dcab0faee70fba717a4a77de50382 (MD5) Previous issue date: 2008en
dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/59406pt_BR
dc.identifier.urihttp://www.repositorio.unicamp.br/handle/REPOSIP/59406-
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/59406-
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.unidadeFaculdade de Ciências Médicaspt_BR
dc.subject.keywordDimerization-
dc.identifier.source18593576-
dc.creator.orcid0000-0002-8426-3136pt_BR
dc.creator.orcid0000-0002-4346-7941pt_BR
dc.creator.orcid0000-0003-2201-8247pt_BR
dc.type.formArtigo originalpt_BR
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