Chemistry:ENX-105

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 D₂ and D₃ receptor antagonist and serotonin 5-HT_1A and 5-HT_2A receptor agonist. Its antagonistic potencies (IC₅₀) are 0.08 nM at the dopamine D_2L receptor, 0.8 nM at the dopamine D_2S receptor, and 3.8 nM at the dopamine D₃ receptor, whereas its activational potencies (EC₅₀) are 5 nM at the serotonin 5-HT_2A receptor and 16 nM at the serotonin 5-HT_1A 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.

See also

• List of investigational hallucinogens and entactogens
• Non-hallucinogenic 5-HT_2A receptor agonist