title: Synergism between topiramate and budipine in refractory status epilepticus in the rat.
abstract: OBJECTIVE
  To evaluate the antiepileptic and neuroprotective properties of topiramate (TPM) alone and with coadministration of the N-methyl-D-aspartate (NMDA)-receptor antagonist budipine in a rat model of refractory status epilepticus.
  
  
  METHODS
  Male Sprague-Dawley rats had electrodes implanted into the perforant path and dentate granule cell layer of the hippocampus under halothane anesthesia. Approximately 1 week after surgery, the perforant path of each animal was electrically stimulated for 2 h to induce self-sustaining status epilepticus. Successfully stimulated rats were given intraperitoneally vehicle (n = 6), TPM (20-320 mg/kg; n = 28), budipine (10 mg/kg; n = 5), or budipine (10 mg/kg) and TPM (80 mg/kg; n = 6) 10 min after the end of the stimulation and monitored behaviorally and electroencephalographically for a further 3 h. The animals were killed 14 days later, and histopathology was assessed.
  
  
  RESULTS
  Neither budipine alone nor TPM at any dose terminated status epilepticus. Despite this, TPM resulted in various degrees of neuroprotection at doses between 40 and 320 mg/kg. Coadministration of budipine with TPM terminated the status epilepticus in all rats. This combination also significantly improved the behavioral profile and prevented status-induced cell death compared with control.
  
  
  CONCLUSIONS
  Budipine and TPM are an effective drug combination in stopping self-sustained status epilepticus, and TPM alone was neuroprotective, despite the continuation of seizure activity.
authors.affiliation: Department of Clinical and Experimental Epilepsy, Institute of Neurology, UCL, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fisher
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Wang
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Cock
authors.forename: Maria
authors.initials: M
authors.lastname: Thom
authors.forename: Philip N
authors.initials: PN
authors.lastname: Patsalos
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019580:Perforant Pathway / Q000473:pathology / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013226:Status Epilepticus / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D000077236:Topiramate; D005632:Fructose; C026710:budipine