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Ganaxolone, a selective, high‐affinity steroid modulator of the γ‐aminobutyric acid‐A receptor, exacerbates seizures in animal models of absence
Author(s) -
Snead O. Carter
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440417
Subject(s) - neuroactive steroid , pentylenetetrazol , allopregnanolone , gabaa receptor , anticonvulsant , pharmacology , medicine , aminobutyric acid , receptor , epilepsy , psychiatry
Ganaxolone (3α‐hydroxy‐3β‐methyl‐5α‐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 γ‐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 γ‐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.