Topiramate blocks perinatal hypoxia-induced seizures in rat pups

Ann Neurol. 2001 Sep;50(3):366-72. doi: 10.1002/ana.1122.


Neonatal seizures caused by hypoxia can be refractory to conventional anticonvulsants. Currently, there is no effective postnatal intervention for newborn infants with hypoxic encephalopathy to prevent brain injury and long-term neurologic sequelae. We previously developed a rat model of perinatal hypoxia-induced seizures with subsequent long-term increases in seizure susceptibility and showed that these epileptogenic effects are selectively blocked by the alpha-amino-3-hydoxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione. Using this model of perinatal seizures, we evaluated the efficacy of topiramate, a structurally novel anticonvulsant drug recently shown to attenuate AMPA/kainate currents. Topiramate effectively suppressed acute seizures induced by perinatal hypoxia in a dose-related manner with a calculated ED50 of 2.1 mg/kg, i.p. Furthermore, in animals that had seizures suppressed by topiramate during acute hypoxia, there were no long-term increases in susceptibility to kainate-induced seizures and seizure-induced neuronal injury. Our results suggest that topiramate may have clinical potential as a therapeutic agent for refractory seizures in human neonates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Suckling
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Convulsants
  • DNA Fragmentation / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fructose / analogs & derivatives
  • Fructose / pharmacology
  • Fructose / therapeutic use*
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hypoxia, Brain / drug therapy*
  • Hypoxia, Brain / pathology
  • Kainic Acid
  • Male
  • Rats
  • Rats, Long-Evans
  • Receptors, AMPA / biosynthesis
  • Receptors, AMPA / drug effects
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Topiramate


  • Anticonvulsants
  • Convulsants
  • Receptors, AMPA
  • Topiramate
  • Fructose
  • Kainic Acid