Antiepileptic potential of ganaxolone

Background/aim. Ganaxolone is an allopregnanolone analogue devoid of hormonal activity which potentiates inhibitory action of GABA through positive allosteric modulation of GABA-A receptor. This review summarizes preclinical and clinical development of ganaxolone for treatment of epilepsy in children and adults. Methods. Published preclinical and clinical studies with ganaxolone were retrieved from multiple searches of MEDLINE and SCINDEKS databases of published scientific articles. Published European and USA patents with ganaxolone were also used as data source for writing this article, as well as the feedback from the company which is developing ganaxolone (Marinus Pharmaceuticals). Results. Ganaxolone prevented seizures in animal models of partial and generalized tonic-clonic seizures, while in the models of absence seizures it was either ineffective or prolonged spike wave discharge. Phase I clinical trials pointed to linear pharmacokinetics of ganaxolone, its high protein-binding and metabolism in the liver, and predominant excretion in feces. Ganaxolone showed certain efficacy as add-on therapy against partial seizures with or without secondary generalization in adult patients and a phase III clinical trial is currently being prepared to test ganaxolone in this indication. Although tried in several small studies on children suffering from infantile spasms, it failed to produce significant response. Conclusions. If future clinical trials confirm efficacy of ganaxolone as add-on therapy in adult patients with partial onset seizures, it could become useful adjunct to existing anti-epileptic therapy of patients who did not achieve satisfactory seizure control. [Projekat Ministarstva nauke Republike Srbije, br. 175007]