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

dc.contributor.authorRamírez Martínez, Juan Francisco
dc.contributor.authorGonzález Chávez, Rodolfo
dc.contributor.authorGuerrero Alba, Raquel
dc.contributor.authorReyes Gutiérrez, Paul Eduardo
dc.contributor.authorMartínez, Roberto
dc.contributor.authorMiranda Morales, Marcela
dc.contributor.authorEspinosa Luna, Rosa
dc.contributor.authorGonzález Chávez, Marco Martín
dc.contributor.authorBarajas López, Carlos
dc.date.accessioned2018-03-23T23:59:41Z
dc.date.available2018-03-23T23:59:41Z
dc.date.issued2013
dc.identifier.citationRamírez-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
dc.identifier.urihttp://hdl.handle.net/11627/3710
dc.description.abstract"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."
dc.publisherMDPI
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectDibenzothiadiazepines
dc.subjectGABAA receptor antagonists
dc.subjectPatch clamp
dc.subjectNeurochemistry
dc.subjectBiological activity
dc.subjectEnteric neurons
dc.subjectElectrophysiology
dc.subject.classificationBIOLOGÍA Y QUÍMICA
dc.titleDibenzo[1,2,5]thiadiazepines are non-competitive GABAA receptor antagonists
dc.typearticle
dc.identifier.doihttp://dx.doi.org/10.3390/molecules18010894
dc.rights.accessAcceso Abierto


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internacional