Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices

Duffy, Steven; Nguyen, Peter V.; Baker, Glen B.

doi:10.1016/j.neuroscience.2004.03.007

Cited by 15 publications

(9 citation statements)

References 60 publications

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“…Other more potent and novel inhibitors of GABA-T are ethanolamine-O-sulfate (EOS), L-cycloserine, and phenylethylidenehydrazine. Interestingly, the latter is used in various psychiatric disorders and increase extracellular GABA concentrations in vivo and decrease epileptiform activity in the rat ex vivo [114]. However, its anticonvulsant properties in vivo varied depending on the seizure model used.…”

Section: Toward Antiepileptic Drugs That Target Tonic Gaba Signalingmentioning

confidence: 99%

Tonic GABAA Receptors as Potential Target for the Treatment of Temporal Lobe Epilepsy

et al. 2015

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Tonic GABAA receptors are a subpopulation of receptors that generate long-lasting inhibition and thereby control network excitability. In recent years, these receptors have been implicated in various neurological and psychiatric disorders, including Parkinson’s disease, schizophrenia, and epilepsy. Their distinct subunit composition and function, compared to phasic GABAA receptors, opens the possibility to specifically modulate network properties. In this review, the role of tonic GABAA receptors in epilepsy and as potential antiepileptic target will be discussed.

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Section: Toward Antiepileptic Drugs That Target Tonic Gaba Signalingmentioning

confidence: 99%

Tonic GABAA Receptors as Potential Target for the Treatment of Temporal Lobe Epilepsy

et al. 2015

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“…The presynaptic effect of STP may be related to its capacity to inhibit GABA‐transaminase (GABA‐T, EC 2.6.1.19), the enzyme responsible for the degradation of GABA (15). Indeed, blocking GABA‐T activity by chemically different drugs invariably increased the amount of GABA in human and rat brain regions (53–56). Likewise, a single in vivo administration of STP increases GABA in the mouse brain (12).…”

Section: Discussionmentioning

confidence: 99%

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Quilichini¹,

Chiron²,

Ben-Ari³

et al. 2006

Epilepsia

142

105

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Summary:Purpose: Stiripentol (STP) is currently an efficient drug for add-on therapy in infantile epilepsies because it improves the efficacy of antiepileptic drugs (AEDs) through its potent inhibition of liver cytochromes P450. In addition, STP directly reduces seizures in several animal models of epilepsy, suggesting that it might also have anticonvulsive effects of its own. However, its underlying mechanisms of action are unknown.Methods: We examined the interactions of STP with γ -aminobutyric acid (GABA) transmission by using patch-clamp methods in CA3 pyramidal neurons in the neonatal rat.Results: STP markedly increased miniature inhibitory postsynaptic current (mIPSC) decay-time constant in a concentrationdependent manner. The prolongation of mIPSC duration does not result from an interaction with GABA transporters because it persisted in the presence of GAT-1 inhibitors (SKF-89976A and NO-711). An interaction with benzodiazepine or neurosteroid binding sites also was excluded because STP-mediated increase of decay time was still observed when these sites were initially saturated (by clobazam, zolpidem, or pregnanolone) or blocked (by flumazenil or dehydroepiandrosterone sulfate), respectively. In contrast, saturating barbiturate sites with pentobarbital clearly occluded this effect of STP, suggesting that STP and barbiturates interact at the same locus. This was directly confirmed by using outside-out patches, because STP increased the duration and not the frequency of opening of GABA A channels.Conclusions: At clinically relevant concentrations, STP enhances central GABA transmission through a barbiturate-like effect, suggesting that STP should possess an antiepileptic effect by itself.

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“…PLZ may reverse the activity of the GABA transporters (GATs), thus exporting GABA from the presynaptic neuron. (29).…”

Section: Klinik Psikofarmakolojimentioning

confidence: 99%

“…Unlike PLZ, PEH has only weak inhibitory effects on MAO (32), suggesting that PEH could be an interesting therapeutic alternative to PLZ in some disorders since it has the GABAergic actions of the parent drug, but would be unlikely to the produce the "cheese effect", a problematic food-drug interaction associated with irreversible inhibitors of MAO . PEH has also been reported to reduce epileptic activity in rat hippocampal slices (29) and, like PLZ, to be neuroprotective in a gerbil transient forebrain ischemia model (33).…”

Section: ß-Phenylethylidenehydrazine (Peh)mentioning

confidence: 99%

Phenelzine: An Old Drug That May Hold Clues to The Development of New Neuroprotective Agents

MacKenzie

Song

Dursun

et al. 2010

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices

Cited by 15 publications

References 60 publications

Tonic GABAA Receptors as Potential Target for the Treatment of Temporal Lobe Epilepsy

Tonic GABAA Receptors as Potential Target for the Treatment of Temporal Lobe Epilepsy

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels

Phenelzine: An Old Drug That May Hold Clues to The Development of New Neuroprotective Agents

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Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices

Cited by 15 publications

References 60 publications

Tonic GABAA Receptors as Potential Target for the Treatment of Temporal Lobe Epilepsy

Tonic GABAA Receptors as Potential Target for the Treatment of Temporal Lobe Epilepsy

Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABAA‐Receptor Channels

Phenelzine: An Old Drug That May Hold Clues to The Development of New Neuroprotective Agents

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Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABA_A‐Receptor Channels