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

Doodipala S. Reddy, Michael A Rogawski

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Ganaxolone (3α-hydroxy-3β-methyl-5α-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 (1.25-20mg/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 6.6mg/kg. The seizure suppression produced by ganaxolone was comparable to that of clonazepam (ED50, 0.1mg/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.

Original languageEnglish (US)
Pages (from-to)254-260
Number of pages7
JournalEpilepsy Research
Volume89
Issue number2-3
DOIs
StatePublished - May 2010

Keywords

  • Amygdala kindling
  • Clonazepam
  • Epilepsy
  • GABA receptor
  • Ganaxolone
  • Neurosteroid

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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