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dc.contributor.author
Pastore, Valentina
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Wasowski, Cristina Lucia N.
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Higgs, Josefina
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Mangialavori, Irene Cecilia
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Bruno Blanch, Luis Enrique
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Marder, Nora Mariel
dc.date.available
2017-06-09T20:34:25Z
dc.date.issued
2014-08
dc.identifier.citation
Pastore, Valentina; Wasowski, Cristina Lucia N.; Higgs, Josefina; Mangialavori, Irene Cecilia; Bruno Blanch, Luis Enrique; et al.; A synthetic bioisoster of trimethadione and phenytoin elicits anticonvulsant effect, protects the brain oxidative damage produced by seizures and exerts antidepressant action in mice; Elsevier Science; European Neuropsychofarmacology; 24; 8; 8-2014; 1405-1414
dc.identifier.issn
0924-977X
dc.identifier.uri
http://hdl.handle.net/11336/17937
dc.description.abstract
Epilepsy is recognized as one of the most common and serious neurological disorder affecting 1–2% of the world׳s population. The present study demonstrates that systemic administration of 3-butyl-5,5-dimethyl-1,2,3-oxathiazolidine-4-one-2,2-dioxide (DIOXIDE), a synthetic compound bioisoster of trimethadione and phenytoin (classical anticonvulsants), elicits a dose dependent anticonvulsant response in mice submitted to the subcutaneous pentylenetetrazole seizure test (scPTZ). Among various factors supposed to play role in epilepsy, oxidative stress and reactive species have strongly emerged. The protection exerted by DIOXIDE over the extent of brain oxidative damage produced by PTZ was determined, by measuring the levels of lipid peroxidation and reduced glutathione and the activity of Na+/K+-ATPase. Psychiatric disorders represent frequent comorbidities in persons with epilepsy. In this report, the potential anxiolytic and antidepressant activities of DIOXIDE were evaluated in several widely used models for assessing anxiolytic and antidepressant activities in rodents. Although DIOXIDE did not evidence anxiolytic activity at the doses tested, it revealed a significant antidepressant-like effect. Preliminary studies of its mechanism of action, by means of its capacity to act via the GABAA receptor (using the [3H]flunitrazepam binding assay in vitro and the picrotoxin test in vivo) and the Na+ channel (using the alkaloid veratrine, a voltage-Na+ channel agonist) demonstrated that the anticonvulsant effect is not likely related to the GABAergic pathway and the antidepressant-like effect could be due to its Na+ channel blocking properties. The results for DIOXIDE suggested it as a new anticonvulsant–antioxidant and antidepressant compound that deserves further development.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
3-Butyl-5,5-Dimethyl-1,2,3-Oxathiazolidine-4-One-2,2-Dioxide
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Anticonvulsant
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Oxidative Damage
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Antidepressant
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Veratrine
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
A synthetic bioisoster of trimethadione and phenytoin elicits anticonvulsant effect, protects the brain oxidative damage produced by seizures and exerts antidepressant action in mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-09T15:02:14Z
dc.journal.volume
24
dc.journal.number
8
dc.journal.pagination
1405-1414
dc.journal.pais
Países Bajos
dc.journal.ciudad
Ámsterdam
dc.description.fil
Fil: Pastore, Valentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.description.fil
Fil: Wasowski, Cristina Lucia N.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.description.fil
Fil: Higgs, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.description.fil
Fil: Mangialavori, Irene Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.description.fil
Fil: Bruno Blanch, Luis Enrique. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Marder, Nora Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
dc.journal.title
European Neuropsychofarmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0924977X14001278
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.euroneuro.2014.04.005
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