Ganaxolone suppression of behavioral and electrographic seizures in the mouse amygdala kindling model

Epilepsy Res. 2010 May;89(2-3):254-60. doi: 10.1016/j.eplepsyres.2010.01.009. Epub 2010 Feb 20.

Abstract

Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a synthetic analog of the endogenous neurosteroid allopregnanolone and a positive allosteric modulator of GABAA receptors, may represent a new treatment approach for epilepsy. Here we demonstrate that pretreatment with ganaxolone (1.25-20 mg/kg, s.c.) causes a dose-dependent suppression of behavioral and electrographic seizures in fully amygdala-kindled female mice, with nearly complete seizure protection at the highest dose tested. The ED50 for suppression of behavioral seizures was 6.6 mg/kg. The seizure suppression produced by ganaxolone was comparable to that of clonazepam (ED50, 0.1 mg/kg, s.c.). To the extent that amygdala kindling represents a model of mesial temporal lobe epilepsy, this study supports the utility of ganaxolone in the treatment of patients with temporal lobe seizures.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiopathology*
  • Animals
  • Anticonvulsants / pharmacology
  • Clonazepam / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Epilepsy, Temporal Lobe / physiopathology
  • Epilepsy, Temporal Lobe / prevention & control*
  • Female
  • Kindling, Neurologic / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Pregnanolone / administration & dosage
  • Pregnanolone / analogs & derivatives*
  • Pregnanolone / pharmacology
  • Seizures / prevention & control*

Substances

  • Anticonvulsants
  • Clonazepam
  • ganaxolone
  • Pregnanolone