ENX-205

ENX-205
Clinical data
Other namesENX205
Routes of
administration		Oral[1]
Drug classDopamine D2 and D3 receptor antagonist; Serotonin 5-HT1A and 5-HT2A receptor agonist; Non-hallucinogenic psychoplastogen
ATC code
  • None

ENX-205 is a drug which is under development for the treatment of mood disorders and post-traumatic stress disorder (PTSD).[1][2][3] It is taken orally.[1]

The drug acts as a dual dopamine D2 and D3 receptor antagonist and serotonin 5-HT1A and 5-HT2A receptor agonist.[1][2][3] The drug is about 10-fold more potent as a dopamine D2 receptor antagonist than as a serotonin 5-HT2A receptor agonist (Ki = 0.04 nM vs. 9.3 nM, respectively; IC50Tooltip half-maximal inhibitory concentration = 0.5 nM vs. EC50Tooltip half-maximal effective concentration = 5 nM, respectively).[3] Accordingly, ENX-205 showed much greater occupancy of the dopamine D2 receptor than the serotonin 5-HT2A receptor in rodents (~66% and ~20%, respectively).[3]

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.[3] 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.[3] The drug has been found to produce antidepressant-like, antianhedonic-like, anxiolytic-like, and prosocial-like effects in rodents.[3]

ENX-205 is under development by Engrail Therapeutics.[1][2] As of December 2025, it is in phase 1 clinical trials for treatment of mood disorders and PTSD.[1][2] The chemical structure of ENX-205 does not yet appear to have been disclosed.[1]

See also

References

  1. ^ a b c d e f g "ENX 205". AdisInsight. 2 December 2025. Retrieved 8 January 2026.
  2. ^ a b c d "ENX-205 Drug Profile". Ozmosi. 1 January 1900. Retrieved 8 January 2026.
  3. ^ a b c d e f g Vadodaria KC, Garvey DS, Kangas B, Brubaker W, McCorvy J, Pizzagalli D, et al. (January 2026). "ACNP 64th Annual Meeting: Poster Abstracts P584-P872". Neuropsychopharmacology. 51 (Suppl 1). Nature Publishing Group: 410–571. doi:10.1038/s41386-025-02281-2. PMC 12783840. PMID 41507446.
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