title: Carisbamate acutely suppresses spasms in a rat model of symptomatic infantile spasms.
abstract: OBJECTIVE
  Infantile spasms are the signature seizures of West syndrome. The conventional treatments for infantile spasms, such as adrenocorticotropic hormone (ACTH) and vigabatrin, are not always effective, especially in symptomatic infantile spasms (SIS). We tested the efficacy of carisbamate, a novel neurotherapeutic drug, to suppress spasms in the multiple-hit rat model of SIS, and compared it with phenytoin to determine if its effect is via sodium-channel blockade.
  
  
  METHODS
  Sprague-Dawley rats received right intracerebral infusions of doxorubicin and lipopolysaccharide at postnatal day 3 (PN3) and intraperitoneal p-chlorophenylalanine at PN5. A single intraperitoneal injection of carisbamate was administered at PN4, after the onset of spasms, at the following doses: 10 mg/kg (CRS-10), 30 mg/kg (CRS-30), and 60 mg/kg (CRS-60), and was compared to vehicle-injected group (VEH). Video-monitoring of PN6-7 CRS-60 or VEH-injected pups was also done.
  
  
  RESULTS
  Carisbamate acutely reduced both behavioral spasms (CRS-30 and CRS-60 groups only) and electroclinical spasms during the first 2-3 postinjection hours, without detectable toxicity or mortality. In contrast, phenytoin (20 or 50 mg/kg) failed to suppress spasms.
  
  
  CONCLUSIONS
  Our findings provide preclinical evidence that carisbamate displays acute anticonvulsive effect on spasms through a sodium channel-independent mechanism. Because spasms in the multiple-hit rat model are refractory to ACTH and transiently sensitive to vigabatrin, carisbamate may constitute a candidate new therapy for SIS, including the ACTH-refractory spasms. Further confirmation with clinical studies is needed.
authors.affiliation: Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ono
authors.forename: Solomon L
authors.initials: SL
authors.lastname: Moshé
authors.forename: Aristea S
authors.initials: AS
authors.lastname: Galanopoulou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002219:Carbamates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010672:Phenytoin / Q000627:therapeutic use; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013035:Spasm / Q000188:drug therapy* / Q000209:etiology; D013036:Spasms, Infantile / Q000150:complications / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; D010672:Phenytoin