Modulation of native GABAA receptor activity by triazolo 1,5-benzodiazepines

Nikas, Periklis; Gatta, Elena; Cupello, A.; Braccio, Mario Di; Grossi, Giancarlo; Pellistri, Francesca; Robello, Mauro

doi:10.1016/j.neuroscience.2013.04.007

Cited by 8 publications

(1 citation statement)

References 34 publications

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“…In previous experiments, we tested these two 1,5-benzodiazepines together with new compounds of that type for their effects on the rapidly desensitizing component of GABA-activated chloride current in cerebellar granule cells (Gatta et al 2010;Nikas et al 2013). In the present study, these two 1,5-benzodiazepines are compared with a classical 1,4-benzodiazepine as diazepam in terms of interaction with specific native GABA A receptors.…”

Section: Introductionmentioning

confidence: 99%

Study of the Interaction of 1,4- and 1,5-Benzodiazepines with GABAA Receptors of Rat Cerebellum Granule Cells in Culture

et al. 2015

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The effects of a classical 1,4-benzodiazepine agonist, such as diazepam, its catabolite N-desmethyl-diazepam (nordiazepam), and 1,5-benzodiazepines such as clobazam and RL 214 (a triazolobenzodiazepine previously synthesized in our labs) were evaluated on native GABAA receptors of cerebellar granule cells in culture. The parameter studied was the increase of GABA-activated chloride currents caused by these substances. The contributions of α6 β2/3 γ2 and α1 α6 β2/3 γ2 receptor subtypes to the increase of GABA-activated chloride current were investigated by comparing the effects of such substances in the presence vs. the absence of furosemide. Furosemide is in fact able to block such receptors. It was found that the percent enhancement of peak GABA-activated current doubled for diazepam, clobazam, and RL 214. However, it did not change for N-desmethyl-diazepam. These results indicate that diazepam, clobazam, and RL 214 interact exclusively with α1 β2/3 γ2 receptors, while N-desmethyl-diazepam seems to interact with not only α1- but also α6-containing receptors.

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Section: Introductionmentioning

confidence: 99%

Study of the Interaction of 1,4- and 1,5-Benzodiazepines with GABAA Receptors of Rat Cerebellum Granule Cells in Culture

et al. 2015

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Recyclable Itaconic Acid with Water as Green Catalytic System: Synthesis of Substituted 1,5‐Benzodiazepine Derivatives at Room Temperature

Tamuli

2020

ChemistrySelect

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The construction of new C-N chemical bonds through cocondensation reaction in water media as sole solvent, especially without the use of any metal catalyst has undergoes green protocols. Herein, we describe a water-mediated and metal-free mild protocol for easily accessing of structurally and electronically diverse 1,5-benzodiazepine analogous by using biode-gradable naturally occurring itaconic acid (20 mol%) in 30 minutes with excellent yields. The simplicity in reaction operation, reusability of the catalytic system and simple filtration to get the desired product make this reaction as "green synthetic pathway" upto multi gram scale level.

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GABAA Receptors of Cerebellar Granule Cells in Culture: Interaction with Benzodiazepines

et al. 2013

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GABA receptor mediated inhibition plays an important role in modulating the input/output dynamics of cerebellum. A characteristic of cerebellar GABA receptors is the presence in cerebellar granule cells of subunits such as α6 and δ which give insensitivity to classical benzodiazepines. In fact, cerebellar GABA receptors have generally been considered a poor model for testing drugs which potentially are active at the benzodiazepine site. In this overview we show how rat cerebellar granule cells in culture may be a useful model for studying new benzodiazepine site agonists. This is based on the pharmacological separation of diazepam-sensitive α1 β2/3 γ2 receptors from those which are diazepam-insensitive and contain the α6 subunit. This is achieved by utilizing furosemide/Zn which block α6 containing and incomplete receptors.

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Modulation of native GABAA receptor activity by triazolo 1,5-benzodiazepines

Cited by 8 publications

References 34 publications

Study of the Interaction of 1,4- and 1,5-Benzodiazepines with GABAA Receptors of Rat Cerebellum Granule Cells in Culture

Study of the Interaction of 1,4- and 1,5-Benzodiazepines with GABAA Receptors of Rat Cerebellum Granule Cells in Culture

Recyclable Itaconic Acid with Water as Green Catalytic System: Synthesis of Substituted 1,5‐Benzodiazepine Derivatives at Room Temperature

GABAA Receptors of Cerebellar Granule Cells in Culture: Interaction with Benzodiazepines

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