Chemistry:6-MeO-isoDMT

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6-MeO-isoDMT, or 6-OMe-isoDMT, also known as 6-methoxy-N,N-dimethylisotryptamine, is a serotonin 5-HT2A receptor agonist, putative serotonergic psychedelic, and psychoplastogen of the isotryptamine group.[1][2][3][4][5] It is the isotryptamine analogue of the psychedelic 5-MeO-DMT and is a positional isomer of the non-hallucinogenic psychoplastogen 5-MeO-isoDMT.[2][6][4][5]

The drug has been found to substitute for DOM and hence to produce hallucinogen-like effects in animal drug discrimination tests.[1][7][5] However, it has greatly reduced hallucinogenic potential in terms of the head-twitch response, a behavioral proxy of psychedelic effects, compared to 5-MeO-DMT.[2][3][4] It has even been described as "non-hallucinogenic" in at least one publication, although this does not strictly seem to be true.[8] Conversely, 6-MeO-isoDMT has comparable psychoplastogenic potency and effects compared to 5-MeO-DMT.[2][3] These effects are blocked by the serotonin 5-HT2A receptor antagonist ketanserin.[3][4] Certain analogues of 6-MeO-isoDMT, like isoDMT, 5-MeO-isoDMT, and zalsupindole (DLX-001; AAZ-A-154; (R)-5-MeO-α-methyl-isoDMT), produce no head-twitch response at all and hence appear to be fully non-hallucinogenic, similarly to 6-MeO-DMT (the tryptamine analogue of 5-MeO-isoDMT).[1][3][4][5] However, like 6-MeO-isoDMT, they retain potent psychoplastogenic effects.[1][3][4]

6-MeO-isoDMT was first described in the scientific literature by 1984.[5][7] It was subsequently further characterized in 2020.[3][4] Confusingly, the drug has been referred to as "5-MeO-isoDMT" (or rather "5-OMe-isoDMT") in some publications.[6]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews 124 (1): 124–163. January 2024. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. 
  2. ↑ 2.0 2.1 2.2 2.3 "The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects". ACS Pharmacology & Translational Science 4 (2): 563–567. April 2021. doi:10.1021/acsptsci.0c00192. PMID 33861218. "[6-MeO-isoDMT] exhibits significantly reduced hallucinogenic potential, as measured by the mouse head-twitch response (HTR) assay, while retaining psychoplastogenic potency comparable to its hallucinogenic congener (Figure 1).31 Because 6-MeO-isoDMT is at least equipotent to 5-MeO-DMT with respect to its ability to promote neural plasticity, it cannot simply be viewed as a less potent hallucinogen. In fact, many of the nonhallucinogenic analogues of psychedelics that our group has developed will not produce hallucinogenic behavioral responses in rodents even at extremely high doses. [...] Figure 1. Hallucinogenic and psychoplastogenic effects can be decoupled through careful chemical design. [...]". 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Development of Non-Hallucinogenic Psychoplastogens". 2022. https://escholarship.org/uc/item/5qr3w0gm. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 "Identification of Psychoplastogenic N,N-Dimethylaminoisotryptamine (isoDMT) Analogues through Structure-Activity Relationship Studies". Journal of Medicinal Chemistry 63 (3): 1142–1155. February 2020. doi:10.1021/acs.jmedchem.9b01404. PMID 31977208. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "Synthesis and evaluation of a novel series of N,N-dimethylisotryptamines". Journal of Medicinal Chemistry 27 (1): 41–45. January 1984. doi:10.1021/jm00367a008. PMID 6581313. 
  6. ↑ 6.0 6.1 "Role of stereochemistry in drug discrimination studies". Drug Discrimination: Applications to Medicinal Chemistry and Drug Studies. Wiley. 5 August 2011. pp. 129–161. doi:10.1002/9781118023150.ch4. ISBN 978-0-470-43352-2. 
  7. ↑ 7.0 7.1 "The Study of Structure-Activity Relationships Using Drug Discrimination Methodology". Methods of Assessing the Reinforcing Properties of Abused Drugs. New York, NY: Springer New York. 1987. pp. 373–390. doi:10.1007/978-1-4612-4812-5_18. ISBN 978-1-4612-9163-3. https://books.google.com/books?id=CIXlBwAAQBAJ&pg=PA379. 
  8. ↑ "Psychedelic innovations and the crisis of psychopharmacology". BioSocieties 19 (1): 37–58. 2024. doi:10.1057/s41292-022-00294-4. ISSN 1745-8552. "[...] David Olson’s laboratory [...] developed the psychedelic 5-Meo-DMT into the supposedly nonpsychedelic 6-Meo-isoDMT, which enhanced neuroplasticity without inducing a head-twitch response in mice. [...] But, since no self-experimental reports on how drugs like 6-Meo-isoDMT [...] affect the human mind have been published and preclinical human trials are still far of, it is not certain whether these drugs are actually free of psychedelic effects, and if they would be clinically efficacious.". 



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