Título

Dibenzo[1,2,5]thiadiazepines are non-competitive GABAA receptor antagonists

Autor

JUAN FRANCISCO RAMIREZ MARTINEZ

RODOLFO GONZALEZ CHAVEZ

RAQUEL GUERRERO ALBA

PAUL EDUARDO REYES GUTIERREZ

ROBERTO MARTINEZ

MARCELA MIRANDA MORALES

ROSA ESPINOSA LUNA

MARCO MARTIN GONZALEZ CHAVEZ

CARLOS BARAJAS LOPEZ

Nivel de Acceso

Acceso Abierto

Licencia

http://creativecommons.org/licenses/by-nc-nd/4.0

Identificador alterno

doi: http://dx.doi.org/10.3390/molecules18010894

Materias

Dibenzothiadiazepines - (AUTOR) GABAA receptor antagonists - (AUTOR) Patch clamp - (AUTOR) Neurochemistry - (AUTOR) Biological activity - (AUTOR) Enteric neurons - (AUTOR) Electrophysiology - (AUTOR) BIOLOGÍA Y QUÍMICA - (CTI)

Resumen o descripción

"A new process for obtaining dibenzo[c,f][1,2,5]thiadiazepines (DBTDs) and their effects on GABAA receptors of guinea pig myenteric neurons are described. Synthesis of DBTD derivatives began with two commercial aromatic compounds. An azide group was obtained after two sequential reactions, and the central ring was closed via a nitrene to obtain the tricyclic sulfonamides (DBTDs). Whole-cell recordings showed that DBTDs application did not affect the holding current but inhibited the currents induced by GABA (IGABA), which are mediated by GABAA receptors. These DBTDs effects reached their maximum 3 min after application and were: (i) reversible, (ii) concentration-dependent (with a rank order of potency of 2c = 2d > 2b), (iii) mediated by a non-competitive antagonism, and (iv) only observed when applied extracellularly. Picrotoxin (which binds in the channel mouth) and DBTDs effects were not modified when both substances were simultaneous applied. Our results indicate that DBTD acted on the extracellular domain of GABAA channels but independent of the picrotoxin, benzodiazepine, and GABA binding sites. DBTDs used here could be the initial model for synthesizing new GABAA receptor inhibitors with a potential to be used as antidotes for positive modulators of these receptors or to induce experimental epilepsy."

Editor

MDPI AG

Fecha de publicación

2013

Tipo de publicación

Artículo

Versión de la publicación

Versión publicada

Recurso de información

http://ipicyt.repositorioinstitucional.mx/jspui/handle/1010/1225

Formato

application/pdf

Idioma

Inglés

Audiencia

Público en general

Sugerencia de citación

Ramírez-Martínez, J., González-Chávez, R., Guerrero-Alba, R., Reyes-Gutiérrez, P., Martínez, R., Miranda-Morales, M., Espinosa-Luna, R., et al. (2013). Dibenzo[1,2,5]thiadiazepines Are Non-Competitive GABAA Receptor Antagonists. Molecules, 18(1), 894–913. MDPI AG. Retrieved from http://dx.doi.org/10.3390/molecules18010894

Repositorio Orígen

Repositorio IPICYT

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