Ganaxolone: a novel positive allosteric modulator of the GABA(A) receptor complex for the treatment of epilepsy.

Ganaxolone is a member of a novel class of neuroactive steroids which modulates the GABA(A) receptor complex (GRC) via an unique recognition site, distinct from those of benzodiazepines and barbiturates. Preclinical data from an array of chemically- and electrically-induced seizure models demonstrate that ganaxolone possesses broad spectrum anticonvulsant activity with potential clinical utility in both generalised and partial seizures, as well as cocaine-induced seizures. Clinical data to date support a favourable safety profile with somnolence, an extension of GABAergic activity, being the most frequently reported adverse event at higher doses. Target indications include infantile spasms and complex partial seizures. Open-label data in paediatric patients with intractable epilepsy suggest that ganaxolone may be effective in treating infantile spasms. A controlled trial utilising an in-patient, monotherapy design demonstrated that ganaxolone effectively decreases complex partial seizure activity compared to placebo. An important area of further evaluation is ganaxolone's potential role in the treatment of women with catamenial epilepsy.