title: Pharmacological considerations in the use of stiripentol for the treatment of epilepsy.
abstract: BACKGROUND
  Despite the fact that more than 20 antiepileptic drugs (AEDs) are currently available, about one-third of patients still present drug resistance. Further efforts are required to develop novel and more efficacious therapeutic strategies, especially for refractory epileptic syndromes showing few and anecdotic therapeutic options.
  
  
  METHODS
  Stiripentol (STP) is a second generation AED that shows GABAergic activity, with immature brain selectivity, and an indirect metabolic action on co-administered AEDs. Two pivotal studies demonstrated STP efficacy in patients with Dravet syndrome with refractory partial seizures, and marketing authorization in Europe, Canada and Japan was granted thereafter. Post-marketing surveys reported a good efficacy and tolerability profile. In addition, interesting data is currently emerging regarding off-label experimentation of STP in other forms of epilepsy.
  
  
  CONCLUSIONS
  STP is an important addition to the limited treatment options available for patients resistant to common AEDs. The possibility to inhibit seizures through the metabolic pathway of lactate dehydrogenase and the inhibitory effects on the entry of Na(+) and Ca(2+) are the most recent findings to emerge about STP and could be proof of its neuroprotective action. Moreover, its positive effects on cognitive function, its good safety and tolerability profile and the increasing data about STP efficacy on other refractory epileptic syndromes may prove to be fertile grounds for further investigation.
authors.affiliation: a Department of Pediatrics , University of L'Aquila , L'Aquila , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Verrotti
authors.affiliation: b Department of Pediatrics , University of Chieti , Chieti , Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Prezioso
authors.affiliation: c Health Science Department , University of Florence , Florence , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Stagi
authors.affiliation: d NESMOS Department, Chair of Pediatrics, Faculty of Medicine and Psychology , Sapienza University , Rome , Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Paolino
authors.affiliation: d NESMOS Department, Chair of Pediatrics, Faculty of Medicine and Psychology , Sapienza University , Rome , Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Parisi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004148:Dioxolanes / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D056687:Off-Label Use
chemical_list: D000927:Anticonvulsants; D004148:Dioxolanes; C021092:stiripentol
keywords: AED; Dravet syndrome; GABA receptors; epilepsy; stiripentol