Stiripentol – characteristic of a new antiepileptic drug

Abstract

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. The drug potently inhibits metabolism of other antiepileptic drugs, significantly elevating their plasma and brain concentrations. This requires dosage adjustments of the concomitant antiepileptic drugs used in combination. In the form of an add-on therapy, stiripentol has proved to be effective in partial and atypical absence epilepsies. Considering its particular efficacy against severe myoclonic seizures in infancy (Dravet's syndrome), stiripentol has been awarded an orphan drug status for an adjunctive therapy of this difficult-to-treat condition.

Anticonvulsant Classes and Possible Mechanism of Actions

“…The antiepileptic properties of stiripentol are attributed to its regulation of the GABAergic system and its ability to hinder certain isoenzymes, such as CYP450, which are involved in the liver metabolism of other antiepileptic medications. This enhances the potency of these drugs . In the year 2000, the European Medical Agency designated stiripentol as an orphan drug, and in January 2007, it was officially registered as an orphan drug in Europe for the treatment of Dravet syndrome as an adjunctive therapy alongside valproate and clobazam .…”

Clinical utility of adjunctive retigabine in partial onset seizures in adults

“…Some of the drugs enhance GABA-mediated inhibition via a direct or indirect influence on GABA A receptors. Direct GABA enhancers, modulating diverse binding sites on the GABA A receptor complex, are benzodiazepines (diazepam, clonazepam), felbamate, phenobarbital, topiramate, and stiripentol 1–3. Other antiepileptics reduce the synaptic GABA uptake (tiagabine) or increase the synaptic GABA concentration through the inhibition of its catabolism (valproate or vigabatrin) 1,2.…”

“…Direct GABA enhancers, modulating diverse binding sites on the GABA A receptor complex, are benzodiazepines (diazepam, clonazepam), felbamate, phenobarbital, topiramate, and stiripentol. 1 – 3 Other antiepileptics reduce the synaptic GABA uptake (tiagabine) or increase the synaptic GABA concentration through the inhibition of its catabolism (valproate or vigabatrin). 1 , 2 Also, antiepileptic drugs may reduce glutamate-mediated excitation via a direct blockade of ionotropic glutamate receptors.…”