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

Summary 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 (1.25–20...

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Bibliographic Details
Published in:Epilepsy research 2010-05, Vol.89 (2), p.254-260
Main Authors: Reddy, Doodipala S, Rogawski, Michael A
Format: Article
Language:English
Subjects:
Amygdala - drug effects
Amygdala - physiopathology
Amygdala kindling
Animals
Anticonvulsants - pharmacology
Biological and medical sciences
Clonazepam
Clonazepam - pharmacology
Disease Models, Animal
Diseases of the nervous system
Dose-Response Relationship, Drug
Epilepsy
Epilepsy, Temporal Lobe - physiopathology
Epilepsy, Temporal Lobe - prevention & control
Female
GABA A receptor
Ganaxolone
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Kindling, Neurologic - drug effects
Medical sciences
Mice
Mice, Inbred C57BL
Nervous system (semeiology, syndromes)
Neurology
Neurosteroid
Pregnanolone - administration & dosage
Pregnanolone - analogs & derivatives
Pregnanolone - pharmacology
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Seizures - prevention & control
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Summary:Summary 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 (1.25–20 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.
ISSN:0920-1211
1872-6844
DOI:10.1016/j.eplepsyres.2010.01.009