title: Effects of carisbamate (RWJ-333369) in two models of genetically determined generalized epilepsy, the GAERS and the audiogenic Wistar AS.
abstract: OBJECTIVE
  The antiepileptic effects of carisbamate were assessed in two models of genetic epilepsy, a model of absence seizures, the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) and a model of convulsive seizures, the Wistar Audiogenic Sensitive (AS) rat.
  
  
  METHODS
  GAERS were equipped with four cortical electrodes over the frontoparietal cortex and the duration of spike-and-wave discharges (SWD) was recorded for 20-120 min. In Wistar AS, the occurrence of, latency to, and duration of wild running and tonic seizures were recorded.
  
  
  RESULTS
  In GAERS, carisbamate (10, 30, and 60 mg/kg) dose dependently reduced the expression of SWD that totally disappeared at the two highest doses by 40 min after injection. SWD duration returned to control levels by 100 min after the injection of 30 mg/kg carisbamate while SWDs were totally suppressed for 120 min after the injection of 60 mg/kg carisbamate. In Wistar AS, 10 mg/kg carisbamate increased the latency to the first running episode and induced the occurrence of a second running episode in three of eight rats. This episode was not present in untreated rats and was indicative of decreased sensitivity to the stimulus. This dose of carisbamate increased by 327% the latency to the tonic seizure that still occurred in the six of eight rats studied. At 20 and 30 mg/kg, no rats exhibited any wild running or tonic seizure.
  
  
  CONCLUSIONS
  The present results support the broad spectrum of antiepileptic activity of carisbamate confirming its efficacy in animal models of primary generalized seizures of both tonic-clonic and of the absence type.
authors.affiliation: INSERM U 398 and 666, Strasbourg, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: François
authors.forename: Any
authors.initials: A
authors.lastname: Boehrer
authors.forename: Astrid
authors.initials: A
authors.lastname: Nehlig
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002219:Carbamates / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data; D004832:Epilepsy, Absence / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D004829:Epilepsy, Generalized / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D020195:Epilepsy, Reflex / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010296:Parietal Lobe / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D000077236:Topiramate