DLX-159

DLX-159 is a putatively non-hallucinogenic psychoplastogen which is under development for the treatment of major depressive disorder and other psychiatric disorders.^[1][3][2] It is taken by mouth.^[1][2]

The full mechanism of action of DLX-159 has yet to be disclosed.^[1][2] The drug shows psychoplastogenic effects in vitro and ex vivo.^[2] These effects are blocked by the serotonin 5-HT_2A receptor antagonst ketanserin as well as by the mTOR inhibitor rapamycin.^[2] It also shows indications of psychoplastogenic effects in vivo in rodents.^[2] In addition, similarly to ketamine, DLX-159 shows rapid antidepressant-like effects in the forced swim test (FST) in rodents that are present within 24 hours of a single dose and are sustained for at least 3 days.^[2] DLX-159 also reversed the depression-like phenotype induced by chronic interferon alpha exposure in rodents.^[2] DLX-159 does not produce the head-twitch response, and hence does not appear to have psychedelic effects.^[2]

DLX-159 shows no signs of cardiotoxicity in preclinical studies.^[2] It was assessed at the serotonin 5-HT_2B receptor and was found to be an antagonist of this receptor.^[2] It is said that further data on the pharmacological activity of DLX-159, including its activities at various receptors and enzymes, will be published in the future.^[2] The drug is orally bioavailable and crosses the blood–brain barrier.^[2]

DLX-159 is under development by Delix Therapeutics.^[1][3][2] As of January 2025, it is in the preclinical research stage of development.^[1][3] The drug was first described in the scientific literature by December 2024.^[2] Its chemical structure does not yet seem to have been disclosed.^[1]

• List of investigational hallucinogens and entactogens
• List of investigational antidepressants
• Tabernanthalog (TBG; DLX-007)
• Zalsupindole (DLX-001; AAZ-A-154)