Mechanism of Action 2018-06-22T10:24:40+00:00

GRX-917 MECHANISM OF ACTION

DUAL MECHANISM OF ACTION

GRX-917 has a dual mechanism of action: A) it works at GABA channels, and B) it increases neurosteroids.

A) Direct actions at GABA Channels

Increased action at GABA channels slows excess neuronal excitation, easing anxiety symptoms. Nonselective, over activation of GABA channels, however, can lead to sedation and other undesired effects. GRX-917 and etifoxine increase activation only at selected subset of GABA channels (channels with β2/3 subunits (Figure A).

Drugs like alcohol, barbiturates, benzodiazepines and Propofol, also work at GABA, but increase action at GABA channels nonselectively, causing sedation and potentially dangerous side effects.

Scientific Explanation: GRX-917 boosts GABAergic transmission via preferential positive allosteric modulation (PAM) of β2/3-subunit-containing GABA receptors, at a binding site distinct from benzodiazepines.

B) Naturally Increases Neurosteroids

GRX-917 and Etifoxine also function as powerful stimulators of neurosteroid biosynthesis, prompting the body to increase the levels of these natural anxiety fighting compounds, like allopregnanolone (ALLO, shown in green in Fig. B)). This is accomplished by increasing activity of a protein called TSPO. The TSPO protein is believed to control the flow of cholesterol into a cellular organelle called the mitochondrion, where it is then converted into neurosteroids, like ALLO.

Endogenous Neurosteroids 

NEUROSTEROIDS NATURALLY ENHANCED

GRX-917 enhances the levels of neurosteroids by increasing the activity of TSPO. The chart compares three of the most well known TSPO compounds for their ability to enhance neurosteroid synthesis activity: etifoxine, XBD173 (aka. Emapunil, AC-5216) and diazepam. The chart demonstrates just how much greater the original (nondeuterated) drug increases neurosteroid synthesis activity, compared to the other well known compounds.

“The most effective known compound to enhance the synthesis of neurosteroids at TSPO.”

Chart Reference: Pharmacopsychiatry Journal, 2015