生物活性

• 描述Stiripentol (STP) is an anticonvulsant agent, which can inhibit N-demethylation of CLB to NCLB mediatated by CYP3A4 (noncompetitively) and CYP2C19 (competitively) with Ki of 1.59±0.07 and 0.516±0.065 μM and IC50 of 1.58 and 3.29 μM, respectively^[2]. Stiripentol used to treat children affected by Dravet syndrome, possibly by inhibiting neuronal lactate dehydrogenase 5 isoenzyme. In vitro, Stiripentol decreased in a dose-dependent manner the synthesis of oxalate by hepatocytes. In vivo, Stiripentol oral administration reduced significantly urine oxalate excretion in rats^[3]. STP potentiates central gamma-aminobutyric acid (GABA) transmission and is characterized by nonlinear pharmacokinetics and inhibition of liver microsomal enzymes^[4]. In a rodent model of SE (status epilepticus), STP terminates behavioral seizures and remains effective in established SE when seizures have become BZD (Benzodiazepines) resistant. The anticonvulsant effects of STP are age dependent, with greater potency in juvenile animals. STP potentiates GABAergic inhibitory postsynaptic currents (IPSCs) and tonic GABAergic currents by acting at a site on the GABAA receptor that is separate from the benzodiazepine binding site^[5]. Stiripentol exhibits higher anticonvulsant properties in the immature than in the mature brain^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03196466	-	-	Recruiting	June 2019	France ... more >> AP-HP Cochin Recruiting Paris, France, 75014 Contact: Jean-Marc Treluyer, M.D., PhD    + 00 1 58 41 28 85    jean-marc.treluyer@parisdescartes.fr Collapse <<
  NCT02926898	Dravet Syndrome	Phase 3	Active, not recruiting	December 2018	United States, California ... more >> University of California San Francisco San Francisco, California, United States, 94143 United States, Colorado The Children'S Hospital Colorado Aurora, Colorado, United States, 80045 United States, Illinois Ann & Robert Lurie Children'S Hospital of Chicago Chicago, Illinois, United States, 60611 United States, Minnesota Mayo Clinic Rochester, Minnesota, United States, 55905 Canada, British Columbia British Columbia Children'S Hospital Vancouver, British Columbia, Canada, V6H3V4 Canada, Quebec Centre Hospitalier Universitaire Sainte-Justine Montreal, Quebec, Canada, H3T 1C5 France Chu Amiens Picardie Service de Neurologie Pediatrique Amiens, France, 80054 CHU DE BORDEAUX Service De Pédiatrie Médicale Bordeaux, France, 33000 CHRU LILLE Centre Hospitalier Régional Universitaire De Lille 2 Lille, France, 59037 HÔPITAL FEMME-MÈRE-ENFANT Hôpital Femme-mère-enfant Service De Neurologie Pédiatrique Lyon, France, 69500 Hôpital La Timone, Service de Neurologie Pédiatrique Marseille, France, 13385 Hôpital Necker Paris, France, 75743 Hôpital Robert Debré Paris, France, 75743 CENTRE REFERENT DES EPILEPSIES Hopital De Hautpierre Strasbourg Cedex, France, F-67098 HÔPITAL DES ENFANTS Pédiatrie Toulouse Cedex 9, France, 31059 Hopital Denfants Chru de Nancy Vandoeuvre Les Nancy Cedex, France, 54511 Germany Krankenhaus Mara Ggmbh, Epilepsiezentrum Bethel Bielefeld, Germany, 33617 Universitätsklinikum Schleswig-Holstein, Klinik Für Neuropädiatrie Kiel, Germany, 24105 Kleinwachau Sächsisches Epilepsiezentrum Radeberg Gemeinnützige Gmbh Radeberg, Germany, 1454 Netherlands Kempenhaeghe Heeze, Netherlands, 5590 Ab Stichting Epilepsie Instellingen Nederland Zwolle, Netherlands, 8025 BV Spain Hospital Sant Joan de Déu Barcelona, Spain, 08950 Hospital Ruber Internacional Primera Planta Servicio de Neurologia Madrid, Spain, 28034 Clinica Universitaria de Navarra Pamplona, Spain, 31008 United Kingdom Institute of Neurosciences Queens Elizabeth University Glasgow, United Kingdom, G51 4TF Alder Hey Children'S Nhs Foundation Trust Liverpool, United Kingdom, L12 2AP Evelina Hospital London, United Kingdom, SE1 7EH Great Ormonnd Street Hospital For Children Nhs Foundation Trust London, United Kingdom, WC1N 3JH Collapse <<
  NCT02607904	Epilepsy	Phase 2	Enrolling by invitation	August 2019	-

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• 参考文献

• [2] Giraud C, Treluyer JM, Rey E, Chiron C, Vincent J, Pons G, Tran A. In vitro and in vivo inhibitory effect of stiripentol on clobazam metabolism. Drug Metab Dispos. 2006 Apr;34(4):608-11

  [3] Le Dudal M, Huguet L, Perez J, Vandermeersch S, Bouderlique E, Tang E, Martori C, Chemaly N, Nabbout R, Haymann JP, Frochot V, Baud L, Deschênes G, Daudon M, Letavernier E. Stiripentol protects against calcium oxalate nephrolithiasis and ethylene glycol poisoning. J Clin Invest. 2019 Apr 4;129(6):2571-2577

  [4] Trojnar MK, Wojtal K, Trojnar MP, Czuczwar SJ. Stiripentol. A novel antiepileptic drug. Pharmacol Rep. 2005 Mar-Apr;57(2):154-60

  [5] Grosenbaugh DK, Mott DD. Stiripentol in refractory status epilepticus. Epilepsia. 2013 Sep;54 Suppl 6:103-5

  [6] Auvin S, Lecointe C, Dupuis N, Desnous B, Lebon S, Gressens P, Dournaud P. Stiripentol exhibits higher anticonvulsant properties in the immature than in the mature rat brain. Epilepsia. 2013 Dec;54(12):2082-90

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