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DLX-159

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From Wikipedia, the free encyclopedia

DLX-159
Clinical data
Other namesDLX159
Routes of
administration		Oral[1][2]
Drug classPsychoplastogen; Serotonin 5-HT2B receptor antagonist; Other undisclosed actions[2]

DLX-159 is a putatively non-hallucinogenic psychoplastogen of the tryptamine family which is under development for the treatment of major depressive disorder and other psychiatric disorders.[1][3][2][4][5][6] It is taken orally.[1][2]

Pharmacology

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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][4][5] These effects are blocked by the serotonin 5-HT2A receptor antagonst ketanserin as well as by the mTOR inhibitor rapamycin.[2][5] 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][4][5] DLX-159 also reversed the depression-like phenotype induced by chronic interferon alpha exposure in rodents.[2][4][5] DLX-159 does not produce the head-twitch response, and hence does not appear to have psychedelic effects.[2][4][5]

DLX-159 shows no signs of cardiotoxicity in preclinical studies.[2] It was assessed at the serotonin 5-HT2B 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]

Research

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DLX-159 is under development by Delix Therapeutics.[1][3][2][4][5] 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] However, it has been disclosed to be a tryptamine derivative.[6]

See also

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References

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  1. 1 2 3 4 5 6 7 "DLX 159". AdisInsight. 15 January 2025. Retrieved 31 January 2025.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Rasmussen K, Agrawal R, Felts A, Leach P, Gillie D, Mungenast A, et al. (2024). "ACNP 63rd Annual Meeting: Poster Abstracts P1-P304: P252. DLX-159: A Novel, Next Generation, Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases" (PDF). Neuropsychopharmacology. 49 (S1): 65–235 (207–207). doi:10.1038/s41386-024-02011-0. ISSN 0893-133X. PMC 11627186. PMID 39643633. Retrieved 31 January 2025.
  3. 1 2 3 "Delving into the Latest Updates on DLX-159 with Synapse". Synapse. 23 January 2025. Retrieved 31 January 2025.
  4. 1 2 3 4 5 6 Qureshi O, Cowley J, Pegg A, Cooper AJ, Gordon J, Brady CA, et al. (July 2025). "Are we hallucinating or can psychedelic drugs modulate the immune system to control inflammation?". Br J Pharmacol. doi:10.1111/bph.70138. PMID 40726049. Delix Therapeutics, a company co-founded by David Olson, have reported in conference abstract form the development of PIPI drugs (e.g. DLX-001 and DLX-159) that display neuroplastogen effects and beneficial activity in animal models of depression without evoking a HTR in rodents (DLX-159; Rasmussen et al., 2024) suggesting a lack of psychedelic activity. [...] Hence, there appears to be clear differential pharmacology of TBG, Br-LSD, IHCH-2079, IHCH 7086, (R)-69, (R)-70, DLX-001 and DLX-159 compared to typical psychedelic compounds (i.e. the listed compounds are predicted to not evoke psychedelic experiences), yet these compounds retain potential therapeutic activity in animal models of psychiatric disease. [...]
  5. 1 2 3 4 5 6 7 Martínez SL (3 December 2025). "The Promise of Non-Hallucinogenic Psychedelics: A Field Coming Into Focus". OPEN Foundation. Retrieved 1 April 2026.
  6. 1 2 "Delix Presents Full Results from Phase 1 Trial of DLX-001 at ACNP Annual Meeting". BioSpace. 12 December 2024. About DLX-159: DLX-159 is a novel, non-hallucinogenic, non-dissociative, tryptamine neuroplastogen being developed for the treatment of Major Depressive Disorder (MDD) and other neuropsychiatric disorders. Preclinical data has demonstrated that DLX-159 increases structural and functional plasticity in prefrontal cortical neurons and has rapid and enduring antidepressant-like effects following a single dose in relevant animal models. Translational preclinical studies demonstrate that DLX-159 elicits a robust signal of CNS engagement. With the promise that DLX-159 holds as a novel treatment for neuropsychiatric conditions, it is being advanced to IND-enabling studies.
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