6-MeO-DMT

6-MeO-DMT
Clinical data
Other names6-Methoxy-N,N-dimethyltryptamine; 6-Methoxy-DMT; 6-Methoxy-N,N-DMT; 6-OMe-DMT
Drug classSerotonin receptor agonist; Non-hallucinogenic serotonin 5-HT2A receptor agonist
Identifiers
  • 2-(6-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine
CAS Number
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC13H18N2O
Molar mass218.300 g·mol−1
3D model (JSmol)
  • CN(C)CCC1=CNC2=C1C=CC(=C2)OC
  • InChI=1S/C13H18N2O/c1-15(2)7-6-10-9-14-13-8-11(16-3)4-5-12(10)13/h4-5,8-9,14H,6-7H2,1-3H3
  • Key:AWOWBKXVYZRYSP-UHFFFAOYSA-N

6-MeO-DMT, or 6-methoxy-N,N-dimethyltryptamine, also known as 6-OMe-DMT, is a serotonergic drug of the tryptamine family.[1][2] It is the 6-methoxy derivative of the serotonergic psychedelic N,N-dimethyltryptamine (DMT) and is a positional isomer of the serotonergic psychedelic 5-MeO-DMT.[3]

Similarly to analogues like DMT and 5-MeO-DMT, 6-MeO-DMT acts as a serotonin 5-HT2A receptor agonist.[1][2] However, in contrast to these agents, but similarly to certain other serotonin 5-HT2A receptor agonists like 6-fluoro-DET, 2-bromo-LSD, lisuride, 25N-N1-Nap, and tabernanthalog, 6-MeO-DMT does not produce the head-twitch response (HTR) or other psychedelic-like effects in animals and hence appears to be non-hallucinogenic.[1][2][4][5] This is thought to be due to biased agonism of the serotonin 5-HT2A receptor; more specifically, weak activation of the Gq pathway with an efficacy for this pathway of less than 70%.[2] However, the non-hallucinogenic nature of 6-MeO-DMT has yet to be confirmed in humans.[6][2]

6-MeO-DMT was first described in the scientific literature by 1968.[7][8][9] It was specifically assessed in a structure–activity relationship (SAR) animal study of serotonergic tryptamines.[7][8] The drug's lack of hallucinogen-like effects in animals, as determined by the HTR, was first described by at least 2020.[2][5]

  1. ^ a b c Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123.
  2. ^ a b c d e f Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nature Communications. 14 (1): 8221. Bibcode:2023NatCo..14.8221W. doi:10.1038/s41467-023-44016-1. PMC 10724237. PMID 38102107.
  3. ^ "2-(6-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine". PubChem. U.S. National Library of Medicine. Retrieved 26 October 2024.
  4. ^ Dunlap LE, Azinfar A, Ly C, Cameron LP, Viswanathan J, Tombari RJ, et al. (February 2020). "Identification of Psychoplastogenic N,N-Dimethylaminoisotryptamine (isoDMT) Analogues through Structure-Activity Relationship Studies". Journal of Medicinal Chemistry. 63 (3): 1142–1155. doi:10.1021/acs.jmedchem.9b01404. PMC 7075704. PMID 31977208.
  5. ^ a b Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, et al. (January 2021). "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature. 589 (7842): 474–479. Bibcode:2021Natur.589..474C. doi:10.1038/s41586-020-3008-z. PMC 7874389. PMID 33299186.
  6. ^ Glennon RA, Dukat M (June 2024). "1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review". ACS Pharmacology & Translational Science. 7 (6): 1722–1745. doi:10.1021/acsptsci.4c00157. PMC 11184610. PMID 38898956.
  7. ^ a b Swonger AK, Rech RH (1978). "Hallucinogens". Psychopharmacology of Aversively Motivated Behavior. Boston, MA: Springer US. pp. 345–383. doi:10.1007/978-1-4684-2394-5_6. ISBN 978-1-4684-2396-9.
  8. ^ a b Gessner PK, Godse DD, Krull AH, McMullan JM (March 1968). "Structure-activity relationships among 5-methoxy-n:n-dimethyltryptamine, 4-hydroxy-n:n-dimethyltryptamine (psilocin) and other substituted tryptamines". Life Sciences. 7 (5): 267–277. doi:10.1016/0024-3205(68)90200-2. PMID 5641719.
  9. ^ Ahlborg U, Holmstedt B, Lindgren JE (1968). "Fate and metabolism of some hallucinogenic indolealkylamines". Pharmacology, Behavior, and Clinical Aspects, Proceedings of a Symposium held at the College of Physicians and Surgeons, Columbia University, New York. Advances in Pharmacology. Vol. 6. pp. 213–229. doi:10.1016/s1054-3589(08)60320-8. ISBN 978-0-12-032906-9. PMID 5658325.