Ganaxolone, a selective, high-affinity steroid modulator of the gamma-aminobutyric acid-A receptor, exacerbates seizures in animal models of absence.

Abstract:

:Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) is a novel neurosteroid which has anticonvulsant properties in a number of seizure models as well as the ability to enhance function of the gamma-aminobutyric acid-A (GABA(A)) receptor complex via a neurosteroid binding site. The object of these experiments was to ascertain the efficacy of ganaxolone against absence seizures. Ganaxolone was assessed in the low-dose pentylenetetrazol (PTZ) and the gamma-hydroxybutyric acid (GHB) model of absence seizures in rats. Ganaxolone pretreatment resulted in a significant prolongation of absence seizure in both the PTZ and GHB models. Further, ganaxolone in doses above 20 mg/kg alone produced bilaterally synchronous spike wave discharges (SWDs) associated with behavioral arrest. These data suggest that augmentation of GABA(A) receptor complex function by neurosteroids has the potential to result in or exacerbate absence seizures.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Snead OC 3rd

doi

10.1002/ana.410440417

subject

Has Abstract

pub_date

1998-10-01 00:00:00

pages

688-91

issue

4

eissn

0364-5134

issn

1531-8249

journal_volume

44

pub_type

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