PRAX-114 is a Novel Extrasynaptic GABA-A Receptor Preferring Positive Allosteric Modulator With a Wide Separation Between a Translational Biomarker Signature Associated With Antidepressant-Like Activity, and Sedative Effects

Alterations in GABAergic transmission contribute to the pathophysiology of major depressive disorder. While benzodiazepine positive allosteric modulators (PAM) of synaptic GABAA receptors (GABAAR) are effective anxiolytics and sedatives, they are not effective antidepressants. Neuroactive steroids like allopregnanolone, which are PAMs of synaptic and extrasynaptic GABAAR have anxiolytic and antidepressant efficacy implicating extrasynaptic GABAAR in mood disorders. The effects of the neuroactive steroid GABAAR-PAM PRAX-114 were assessed on behavioral and translational endpoints.