Ganaxolone

Ganaxolone (developmental code name CCD-1042) is an experimental drug which is under development by Marinus Pharmaceuticals for potential medical use as an anxiolytic and anticonvulsant. Ganaxolone has been shown to protect against seizures in animal models, and to act a positive allosteric modulator of the GABAA receptor.
Ganaxolone is being investigated for potential medical use in the treatment of epilepsy. It is well tolerated in human trials, with the most commonly reported side effects being somnolence (sleepiness), dizziness, and fatigue. Trials in adults with focal onset seizures and in children with infantile spasms have recently been completed. There are ongoing studies in patients with focal onset seizures, PCDH19 pediatric epilepsy, and behaviors in Fragile X syndrome.
Pharmacology.
Mechanism of action.
The exact mechanism of action for ganaxolone is unknown; however, results from animal studies suggest that it acts by blocking seizure propagation and elevating seizure thresholds.
Ganaxolone is thought to modulate both synaptic and extrasynaptic GABAA receptors to normalize over-excited neurons. Ganaxolone's activation of the extrasynaptic receptor is an additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increase GABA signaling.
Ganaxolone binds to allosteric sites of the GABAA receptor to modulate and open the chloride ion channel, resulting in a hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission, reducing the chance of a successful action potential (depolarization) from occurring.
Clinical trials.
The most common adverse events reported across clinical trials have been somnolence (sleepiness), dizziness, and fatigue. In 2015, the MIND Institute at the University of California, Davis, announced that it was conducting, in collaboration with Marinus Pharmaceuticals, a randomized, placebo-controlled, Phase 2 clinical trial evaluating the effect of ganaxolone on behaviors associated with Fragile X syndrome in children and adolescents.
Chemistry.
Ganaxolone is a synthetic pregnane steroid. Other pregnane neurosteroids include alfadolone, alfaxolone, allopregnanolone (brexanolone), hydroxydione, minaxolone, pregnanolone (eltanolone), and renanolone, among others.