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

@article{Quilichini2006StiripentolAP,
  title={Stiripentol, a Putative Antiepileptic Drug, Enhances the Duration of Opening of GABAA‐Receptor Channels},
  author={Pascale P. Quilichini and Catherine Chiron and Yehezkel Ben-Ari and Henri Gozlan},
  journal={Epilepsia},
  year={2006},
  volume={47}
}
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. 

Stiripentol in the Management of Epilepsy

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The effects of stiripentol on GABAA receptors

Positive modulation by stiripentol was most effective at GABAA receptors containing an α3 subunit, which is developmentally regulated, with highest levels in the immature brain, and may explain the greater clinical efficacy of stiripENTol in childhood‐onset epilepsies, including Dravet syndrome.

Characterization of the Anticonvulsant, Behavioral and Pharmacokinetic Interaction Profiles of Stiripentol in Combination with Clonazepam, Ethosuximide, Phenobarbital, and Valproate Using Isobolographic Analysis

Isobolographic analysis was used to characterize the interactions between stiripentol and clonazepam, ethosuximide, EMT, phenobarbital, and valproate in suppressing pentylenetetrazole‐induced clonic seizures in mice.

Interactions between modulators of the GABA(A) receptor: Stiripentol and benzodiazepines.

  • J. Fisher
  • Biology, Medicine
    European journal of pharmacology
  • 2011

Stiripentol – characteristic of a new antiepileptic drug

Stiripentol represents a group of drugs indirectly enhancing GABA-ergic neurotransmission and it exerts a protective activity in some experimental seizure models, including maximal electroshock (MES)-, pentylenetetrazol-, bicuculline-, strychnine-, and cocaine-induced convulsions.

Mechanisms of action of antiepileptic drugs

The proposed mechanisms of action of marketed AEDs in the US are reviewed, the future of Aeds in development is discussed and the proposed targets of action at more than one molecular target are discussed.

Mechanisms of action of currently used antiseizure drugs

Stiripentol exhibits higher anticonvulsant properties in the immature than in the mature rat brain

After the first positive experimental data in rodents in the early 1970s demonstrating the anticonvulsant effect of stiripentol (STP), in vitro studies showed that STP acts directly on γ‐aminobutyric acid A (GABAA) receptors, leading to the hypothesis thatSTP might exhibit higher efficacy in the immature brain.
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