Ganaxolone treatment for epilepsy patients: from pharmacology to place in therapy

Introduction: Nonsulfated neurosteroids can provide phasic and tonic inhibition through activation of synaptic and extra-synaptic γ-aminobutyric acid (GABA)A receptors, exhibiting a greater potency for the latter. These actions occur by interacting with modulatory sites that are distinct from those bound by benzodiazepines and barbiturates. Ganaxolone (GNX) is a synthetic analog of the endogenous neurosteroid allopregnanolone and a member of a novel class of neuroactive steroids called epalons. Areas covered: The authors review the pharmacology of GNX, summarize the main clinical evidence about its antiseizure efficacy and tolerability, and suggest implications for clinical practice and future research. Expert opinion: The clinical development of GNX is mainly oriented to target unmet needs and focused on status epilepticus and rare genetic epilepsies that have few or no treatment options. The availability of oral and intravenous formulations allows reaching adult and pediatric patients in acute and chronic care settings. Further evidence will complement the understanding of the potentialities of GNX and possibly lead to indications for use in clinical practice.