Deuterated etifoxine

Deuterated etifoxine (developmental code name GRX-917) is a deuterated drug which is under development for the treatment of anxiety disorders and mood disorders.

Drug development
It was originated by GABA Therapeutics and is under development by GABA Therapeutics and ATAI Life Sciences.

Chemistry
Deuterated etifoxine is a deuterated form of etifoxine (Stresam) with improved pharmacokinetic properties, for instance a longer elimination half-life and duration of action. Etifoxine has been widely used as an anxiolytic for many decades.

Biology
Etifoxine and deuterated etifoxine are GABAA receptor positive allosteric modulators (GABAkines) and ligands of the translocator protein (TSPO), both of which may contribute to anxiolytic effects. The TSPO promotes steroidogenesis of inhibitory neurosteroids such as allopregnanolone, which act as potent GABAA receptor positive allosteric modulators, and hence interactions with the TSPO can also indirectly potentiate the GABAA receptor. The precise isotopic substitution of deuterated etifoxine has not yet been disclosed. As of January 2023, deuterated etifoxine is in phase 1 clinical trials for anxiety disorders and preclinical development for mood disorders.