Chemical Name: Zuranolone (SAGE-217,CS-2797,BIIB125)
CAS No.: 1632051-40-1
Mechanism: GABAA receptor modulator
Status: Phase III
Developer: Sage Therapeutics
Sage -217 is an investigational chemical developed by Sage Therapeutics for the treatment of major depressive disorder and postpartum depression, as well as primary tremor in Parkinson's disease, insomnia, and epilepsy. According to Sage Therapeutics, Sage -217 is a synthetic pregnane neurosteroid, which is an orthosteric modulator of the GABAA receptor.The goal of SAGE-217 is to improve upon and succeed Brexanolone - another Sage treatment for depression that is currently in clinical trials. In the phase 3 trial ROBIN for the treatment of women with postpartum depression (PPD) patients, the primary and secondary endpoints of the trial were met. Failed in Phase 3 for major depression.
Chemical Identity: Synthetic neuroactive steroid Zuranolone, often referred to as SAGE-217, acts as a positive allosteric modulator of the GABA_A (gamma-aminobutyric acid) receptor. Its molecular formula is C25H35NO2, and it is a member of the GABA receptor modulator class of substances, which interacts with the central nervous system (CNS)'s inhibitory neurotransmitter GABA. Its structural ancestry is in the natural neurosteroid allopregnanolone, but it has been modified to improve its pharmacokinetic characteristics and make it more orally bioavailable.
Mechanism of Action: GABA is the main inhibitory neurotransmitter in the central nervous system. Zuranolone enhances the inhibitory effects of GABA by acting as a strong positive allosteric modulator of GABA_A receptors. Zuranolone enhances the GABA_A receptor's response by binding to particular locations on the receptor, which causes the cell to become more hyperpolarized and less excitable. This modulation has a soothing, anxiolytic, and anticonvulsant effect, which makes it useful in the treatment of conditions including postpartum depression (PPD) and major depressive disorder (MDD). Because of its effects on the GABAergic system, it aids in reestablishing the equilibrium between excitation and inhibition in neural circuits, which can be upset in depressive conditions.
