ENX-205
ENX-205 is a drug which is under development for the treatment of mood disorders and post-traumatic stress disorder. It is taken orally.
The drug acts as a dual dopamine D2 and D3 receptor antagonist and serotonin 5-HT1A and 5-HT2A receptor agonist. The drug is about 10-fold more potent as a dopamine D2 receptor antagonist than as a serotonin 5-HT2A receptor agonist. Accordingly, ENX-205 showed much greater occupancy of the dopamine D2 receptor than the serotonin 5-HT2A receptor in rodents.
The drug is described as a non-hallucinogenic psychoplastogen via its serotonin 5-HT2A 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 D2 and D3 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.