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6-Hydroxy-DMT

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6-Hydroxy-DMT
Clinical data
Other names6-HDMT; 6-HO-DMT; 6-OH-DMT; 6-Hydroxy-N,N-dimethyltryptamine
Drug classSerotonin receptor modulator
ATC code
  • None
Identifiers
  • 3-[2-(dimethylamino)ethyl]-1H-indol-6-ol
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC12H16N2O
Molar mass204.273 g·mol−1
3D model (JSmol)
  • CN(C)CCC1=CNC2=C1C=CC(=C2)O
  • InChI=1S/C12H16N2O/c1-14(2)6-5-9-8-13-12-7-10(15)3-4-11(9)12/h3-4,7-8,13,15H,5-6H2,1-2H3
  • Key:WUQMRWPLIMXBDX-UHFFFAOYSA-N

6-Hydroxy-DMT, also known as 6-hydroxy-N,N-dimethyltryptamine, is a serotonin receptor modulator of the tryptamine family.[1][2][3][4][5] It is a major metabolite of the psychedelic drug dimethyltryptamine (DMT) in rodents but a minor metabolite of DMT in humans.[4][6][7] It is the 6-hydroxy analogue of DMT and a positional isomer of bufotenin (5-hydroxy-DMT) and psilocin (4-hydroxy-DMT).[2][3][8]

The drug was completely inactive in terms of psychoactive and autonomic effects at doses of 0.75 to 1 mg/kg (~53–70 mg for a 70-kb person) by intramuscular injection in humans.[1][2][5] The drug was said to be indistinguishable from placebo.[5] Conversely, DMT produced strong hallucinogenic effects at the same doses.[5] However, 6-hydroxy-DMT has been found to produce pharmacological effects in animals, albeit with diminished potency compared to DMT.[4][2][8][9] As examples, in terms of behavioral effects, 6-hydroxy-DMT was ≥3-fold less potent in rats, >10-fold less potent in cats, and 3-fold less potent in monkeys.[4] It was suggested by Richard Glennon and colleagues that the reduced activity of 6-hydroxy-DMT may be due to its greater hydrophilicity and reduced ability to penetrate the blood–brain barrier analogously to the case of bufotenin.[8]

Subsequent research assessed 6-hydroxy-DMT at the serotonin receptors in vitro.[7] It was found to have detectable but very low affinity for the serotonin 5-HT2 receptors (Ki ≥ 6,300–19,000 nM).[7]

6-Hydroxy-DMT was first described in the scientific literature by at least 1962.[10]

See also

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References

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  1. ^ a b Shulgin, Alexander; Shulgin, Ann (September 1997). TiHKAL: The Continuation. Berkeley, California: Transform Press. ISBN 0-9630096-9-9. OCLC 38503252. "6-HO-DMT is a minor metabolite of DMT in man, and it was studied for the same reasons. Could this compound play a role in explaining the activity of the parent dialkylamine? It was explored in a series of subjects who had responded spectacularly to DMT. The five volunteers in this study were former opium addicts who were serving sentences for violation of United States narcotics laws. They were administered 6-HO-DMT at either 0.75 mg/kg (one subject) or 1.0 mg/kg (four subjects) and reported no differences from the inactive placebo control. The objective measures (blood pressure, respiration and heart rate, pupillary dilation) confirmed this absence of activity at this level. The active control drug was DMT itself, and it showed the expected responses in all regards." [...] "It is pretty generally accepted that 6-HO-DMT is inactive. I am not too surprised. There are so few things with open and exposed hydroxyl groups that succeed in making it through the lipid barriers that protect to the brain."
  2. ^ a b c d Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. In fact, animal studies with 6-hydroxy-N,N-dimethyltryptamine suggested that the compound was indeed more potent that its parent (Szara and Hearst, 1962). [...] 6-Hydroxy-5-methoxy-N,Ndiniethyltryptamine [(XXXV), R1 = OCH3 , R 2 = R3 = CH3] appeared to be less potent than 5-methoxy-N,N-dimethyltryptamine (Taborsky et al., 1966) and 6-hydroxy-5-methoxytryptamine [(XXXV), R1 = OCH3 , R2 = R3 = H] was less potent than 5-methoxytryptamine (Taborsky et al., 1965). In animal studies (Uyeno, 1969) as well as human studies (Rosenberg et al., 1963), 6-hydroxy-N,N-dimethyltryptamine [(XXXV), R 1 = H, R2 = R3 = CH3] was inactive at 1 mgfkg, whereas N,N-dimethyltryptamine is clinically effective at this dosage. [...] The present evidence indicates that chemical substitution on the 6 position of the tryptamine system destroys the psychotomimetic potential of the compound.
  3. ^ a b Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Retrieved 1 February 2025.
  4. ^ a b c d Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M.
  5. ^ a b c d Rosenberg DE, Isbell H, Miner EJ (February 1963). "Comparison of a placebo, N-dimethyltryptamine, and 6-hydroxy-N-dimethyltryptamine in man". Psychopharmacologia. 4: 39–42. doi:10.1007/BF00429362. PMID 14050410.
  6. ^ Barker SA, Monti JA, Christian ST (1981). "N, N-dimethyltryptamine: an endogenous hallucinogen". Int Rev Neurobiol. 22: 83–110. doi:10.1016/s0074-7742(08)60291-3. PMID 6792104.
  7. ^ a b c Sard H, Kumaran G, Morency C, Roth BL, Toth BA, He P, Shuster L (October 2005). "SAR of psilocybin analogs: discovery of a selective 5-HT 2C agonist". Bioorg Med Chem Lett. 15 (20): 4555–4559. doi:10.1016/j.bmcl.2005.06.104. PMID 16061378.
  8. ^ a b c Glennon RA, Rosecrans JA (1982). "Indolealkylamine and phenalkylamine hallucinogens: a brief overview". Neurosci Biobehav Rev. 6 (4): 489–497. doi:10.1016/0149-7634(82)90030-6. PMID 6757811. 6-Hydroxy DMT (3f) displays only weak behavioral activity in animals [10, 73, 74] and is not hallucinogenic in man [55]. It may be argued that the lipid solubility of 6-hydroxy DMT, like that of bufotenine, will not allow it to penetrate into the brain; this might account for its inactivity. [...] It might be speculated that 6-hydroxy DMT, like bufotenine, would display more activity if it were made more lipid soluble by, for example, acylation of the hydroxyl group. Although this is an intriguing possibility, its likelihood is not supported by the low order of activity of its O-methyl ether 6-OMe DMT (3g) [20,27].
  9. ^ Uyeno ET (1971). "Relative potency of amphetamine derivatives and N,N-dimethyltryptamines". Psychopharmacologia. 19 (4): 381–387. doi:10.1007/BF00404382. PMID 5565249.
  10. ^ Szara, S.; Hearst, E.; Putney, F. (1962). "Metabolism and behavioural action of psychotropic tryptamine homologues". International Journal of Neuropharmacology. 1 (1–3): 111–117. doi:10.1016/0028-3908(62)90015-1.
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