ENX-105 is an investigational new drug being developed by Engrail Therapeutics for the treatment of post-traumatic stress disorder (PTSD). It is currently in the preclinical stage, trailing behind a closely related Engrail compound, ENX-104, which is focused on depression and anhedonia.
The drug is described as a dopamine D<sub>2</sub> and D<sub>3</sub> receptor antagonist and serotonin 5-HT<sub>1A</sub> and 5-HT<sub>2A</sub> receptor agonist. Its antagonistic potencies () are 0.08nM at the dopamine D<sub>2L</sub> receptor, 0.8nM at the dopamine D<sub>2S</sub> receptor, and 3.8nM at the dopamine D<sub>3</sub> receptor, whereas its activational potencies () are 5nM at the serotonin 5-HT<sub>2A</sub> receptor and 16nM at the serotonin 5-HT<sub>1A</sub> receptor.
ENX-105 does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence is putatively non-hallucinogenic. The drug has shown anxiolytic-, antipsychotic-, anti-anhedonic-, and pro-cognitive-like effects in rodents. It has also been found to increase dopamine levels in the nucleus accumbens in rodents.
As with ENX-104, ENX-105 is a deuterated enantiomer of nemonapride.