ENX-205 is a drug which is under development for the treatment of mood disorders and post-traumatic stress disorder (PTSD). It is taken orally.
The drug acts as a dual 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. The drug is about 10-fold more potent as a dopamine D<sub>2</sub> receptor antagonist than as a serotonin 5-HT<sub>2A</sub> receptor agonist (K<sub>i</sub> = 0.04nM vs. 9.3nM, respectively; = 0.5nM vs. = 5nM, respectively). Accordingly, ENX-205 showed much greater occupancy of the dopamine D<sub>2</sub> receptor than the serotonin 5-HT<sub>2A</sub> receptor in rodents (~66% and ~20%, respectively).
The drug is described as a non-hallucinogenic psychoplastogen via its serotonin 5-HT<sub>2A</sub> receptor agonism, with the drug failing to produce the head-twitch response but robustly enhancing neuroplasticity in preclinical research. In addition, it increases dopamine levels in the nucleus accumbens and prefrontal cortex in rodents, consistent with presynaptic dopamine D<sub>2</sub> and D<sub>3</sub> receptor antagonism and possible disinhibition of dopaminergic signaling within these areas. The drug has been found to produce antidepressant-like, antianhedonic-like, anxiolytic-like, and prosocial-like effects in rodents.
ENX-205 is under development by Engrail Therapeutics. As of December 2025, it is in phase 1 clinical trials for treatment of mood disorders and PTSD. The chemical structure of ENX-205 does not yet appear to have been disclosed.