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AAZ-A-154

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Not to be confused with DLX1.
AAZ-A-154
Clinical data
Other namesAAZ; DLX-001; DLX-1; DLX001; DLX1; (R)-5-Methoxy-N,N-dimethyl-α-methylisotryptamine; (R)-5-MeO-α-methyl-isoDMT; (R)-5-MeO-N,N-dimethyl-isoAMT
Drug classNon-hallucinogenic serotonin 5-HT2A receptor agonist; Psychoplastogen
Identifiers
  • (2R)-1-(5-methoxy-1H-indol-1-yl)-N,N-dimethylpropan-2-amine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H20N2O
Molar mass232.327 g·mol−1
3D model (JSmol)
  • CN(C)[C@H](C)Cn1ccc2cc(ccc21)OC
  • InChI=1S/C14H20N2O/c1-11(15(2)3)10-16-8-7-12-9-13(17-4)5-6-14(12)16/h5-9,11H,10H2,1-4H3/t11-/m1/s1
  • Key:KHEUWLQKCXGVEL-LLVKDONJSA-N

AAZ-A-154, also known as DLX-001 or as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine, is a novel isotryptamine derivative which acts as a serotonin 5-HT2A receptor agonist discovered and synthesized by the lab of Professor David E. Olson at the University of California, Davis.[1][2][3][4] It is being developed for the treatment of major depressive disorder and other central nervous system disorders.[1][2]

Animal studies suggest that it produces antidepressant effects without the psychedelic action typical of drugs from this class.[5][6][3][4] In tests, AAZ-A-154 had antidepressant-like effects in mice without causing the head-twitch response linked to hallucinogenic effects.[7][3][4] Due to the rapidly-induced and enduring neuroplasticity, AAZ-A-154 is a member of the class of compounds known as non-hallucinogenic psychoplastogens.[8][3][4]

The drug is selective for the serotonin 5-HT2 receptors.[9] It is an antagonist of the serotonin 5-HT2B receptor and showed no cardiovascular safety signals in animals.[4] AAZ-A-154 is orally bioavailable and centrally penetrant in animals.[4]

AAZ-A-154, as well as related compounds, are licensed by Delix Therapeutics and are being developed as potential medicines for neuropsychiatric disorders.[8][1][2] As of December 2023, AAZ-A-154, under the code name DLX-001, is in phase 1 clinical trials for major depressive disorder and other central disorders.[1][2]

See also

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References

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  1. ^ a b c d "DLX 1". AdisInsight. 11 December 2023. Retrieved 2 November 2024.
  2. ^ a b c d "Delving into the Latest Updates on DLX-001 with Synapse". Synapse. 1 November 2024. Retrieved 2 November 2024.
  3. ^ a b c d Rasmussen K, Chytil M, Agrawal R, Leach P, Gillie D, Mungenast A, et al. (2024). "14. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases". Biological Psychiatry. 95 (10). Elsevier BV: S80. doi:10.1016/j.biopsych.2024.02.192. ISSN 0006-3223.
  4. ^ a b c d e f Rasmussen K, Engel S, Chytil M, Koenig A, Meyer R, Rus M, et al. (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 - P500: P361. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (274–275). doi:10.1038/s41386-023-01756-4. PMC 10729596. PMID 38040810.
  5. ^ Dong C, Ly C, Dunlap LE, Vargas MV, Sun J, Hwang IW, et al. (May 2021). "Psychedelic-inspired drug discovery using an engineered biosensor". Cell. 184 (10): 2779–2792.e18. doi:10.1016/j.cell.2021.03.043. PMC 8122087. PMID 33915107.
  6. ^ WO 2020176597, Olson DE, Dunlap L, Wagner FF, "N-substituted indoles and other heterocycles for treating brain disorders", published 3 September 2020, assigned to The Regents of the University of California 
  7. ^ Cross R (2021-09-27). "Delix raises $70 million to synthesize psychedelic-inspired drugs". cen.acs.org. Archived from the original on 2021-09-27. Retrieved 2022-01-14.
  8. ^ a b "Can we take the high out of psychedelics?". Wired UK. ISSN 1357-0978. Retrieved 2022-07-07.
  9. ^ Dunlap LE (2022). Development of Non-Hallucinogenic Psychoplastogens (Thesis). University of California, Davis. Retrieved 18 November 2024.


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