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]
 | |
| Clinical data | |
|---|---|
| Other names | AAZ; 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 class | Non-hallucinogenic serotonin 5-HT2A receptor agonist; Psychoplastogen |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C14H20N2O |
| Molar mass | 232.327 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
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 is a member of the isotryptamine group of compounds. It is a combined derivative of isoDMT, 5-MeO-isoDMT, and isoAMT. Another related compound is 6-MeO-isoDMT.
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
editReferences
edit- ^ a b c d "DLX 1". AdisInsight. 11 December 2023. Retrieved 2 November 2024.
- ^ a b c d "Delving into the Latest Updates on DLX-001 with Synapse". Synapse. 1 November 2024. Retrieved 2 November 2024.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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
- ^ 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.
- ^ a b "Can we take the high out of psychedelics?". Wired UK. ISSN 1357-0978. Retrieved 2022-07-07.
- ^ Dunlap LE (2022). Development of Non-Hallucinogenic Psychoplastogens (Thesis). University of California, Davis. Retrieved 18 November 2024.