AAZ-A-154

Last updated
AAZ-A-154
AAZ-A-154.svg
Identifiers
  • (2R)-1-(5-methoxy-1H-indol-1-yl)-N,N-dimethylpropan-2-amine
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H20N2O
Molar mass 232.327 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 is a novel isotryptamine derivative which acts as a 5-HT2A receptor agonist discovered and synthesized by the lab of Professor David E. Olson at UCDavis. Animal studies suggest that it produces antidepressant effects without the psychedelic action typical of drugs from this class. [1] [2] In tests, AAZ-A-154 had antidepressant effects in mice without causing the head-twitch response linked to hallucinogenic effects. [3] Due to the rapidly-induced and enduring neuroplasticity, AAZ-A-154 is a member of the class of compounds known as non-hallucinogenic psychoplastogens. [4] This compound, as well as related compounds, are licensed by Delix Therapeutics and are being developed as potential medicines for neuropsychiatric disorders. [4]

See also

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Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

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5-HT<sub>2A</sub> receptor Subtype of serotonin receptor

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Psychoplastogens are a group of small molecule drugs that produce rapid and sustained effects on neuronal structure and function, intended to manifest therapeutic benefit after a single administration. Several existing psychoplastogens have been identified and their therapeutic effects demonstrated; several are presently at various stages of development as medications including ketamine, MDMA, scopolamine, and the serotonergic psychedelics, including LSD, psilocin, DMT, and 5-MeO-DMT. Compounds of this sort are being explored as therapeutics for a variety of brain disorders including depression, addiction, and PTSD. The ability to rapidly promote neuronal changes via mechanisms of neuroplasticity was recently discovered as the common therapeutic activity and mechanism of action.

David E. Olson is an American chemist and neuroscientist. He is an associate professor of chemistry, biochemistry and molecular medicine at the University of California, Davis, and is the founding director of the UC Davis Institute for Psychedelics and Neurotherapeutics.

Delix Therapeutics is an American biotech company based in Boston, Massachusetts. The company develops novel neuroplasticity-promoting therapeutics for central nervous system (CNS) diseases such as depression and post-traumatic stress disorder (PTSD). It was co-founded in 2019 by David E. Olson and Nick Haft.

<span class="mw-page-title-main">6-Fluoro-DET</span> Chemical compound

6-Fluoro-DET is a substituted tryptamine derivative related to drugs such as DET and 5-fluoro-DET. It acts as a partial agonist at the 5-HT2A receptor, but while it produces similar physiological effects to psychedelic drugs, it does not appear to produce psychedelic effects itself even at high doses. For this reason it saw some use as an active placebo in early clinical trials of psychedelic drugs but was regarded as having little use otherwise, though more recent research into compounds such as AL-34662, TBG and AAZ-A-154 has shown that these kind of non-psychedelic 5-HT2A agonists can have various useful applications.

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Lin Tian is a Chinese-American neuroscientist and biochemist. She is a Scientific Director of the Max Planck Florida Institute for Neuroscience in Jupiter, FL, and was formerly a professor in the Department of Biochemistry and Molecular Medicine at the University of California, Davis. Tian is known for her research in the fields of neuroscience and biochemical engineering. She develops and applies molecular tools to understand brain function and dysfunction at the individual, neuronal level.

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<span class="mw-page-title-main">IHCH-7086</span> Chemical compound

IHCH-7086 is a drug which acts as an agonist at the 5-HT2A serotonin receptor. It was derived by structural simplification of the 5-HT2A antagonist atypical antipsychotic drug lumateperone along with several related compounds such as IHCH-7079, which was found to be a non-hallucinogenic biased 5-HT2A agonist that was active in antidepressant assays but did not produce psychedelic-like responding in mice. The related structure IHCH-7113 was found to produce a positive head-twitch response in mice, suggesting likely hallucinogenic activity in humans.

References

  1. Dong C, Ly C, Dunlap LE, Vargas MV, Sun J, Hwang IW, Azinfar A, Oh WC, Wetsel WC, Olson DE, Tian L (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.
  2. 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
  3. Cross, Ryan (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.
  4. 1 2 "Can we take the high out of psychedelics?". Wired UK. ISSN   1357-0978 . Retrieved 2022-07-07.