UCD0179

UCD0179
Clinical data
Other names4-Desmethylene-LSD; 4-Nor-LSD; 3,5-Seco-LSD; Des-C-LSD; UCD0179; UCD-0179; DEIMDHPCA; "Compound 11"
Drug classSerotonin 5-HT2 receptor agonist; Psychoplastogen; Simplified/partial LSD analogue
ATC code
  • None
Identifiers
  • (3R)-N,N-diethyl-5-(1H-indol-4-yl)-1-methyl-3,6-dihydro-2H-pyridine-3-carboxamide
CAS Number
PubChem CID
Chemical and physical data
FormulaC19H25N3O
Molar mass311.429 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)[C@H]1CN(CC(=C1)C2=C3C=CNC3=CC=C2)C
  • InChI=1S/C19H25N3O/c1-4-22(5-2)19(23)15-11-14(12-21(3)13-15)16-7-6-8-18-17(16)9-10-20-18/h6-11,15,20H,4-5,12-13H2,1-3H3/t15-/m1/s1
  • Key:GDCMLRPQENDWLG-OAHLLOKOSA-N

UCD0179, also known as 4-desmethylene-LSD or 3,5-seco-LSD, is an indole derivative and a "partial" or simplified lysergamide which is closely related to the highly potent serotonergic psychedelic lysergic acid diethylamide (LSD). It is specifically the analogue of LSD in which one of LSD's carbon atoms in the ergoline ring system, the carbon at position 4, has been removed. This in turn renders the molecule more flexible and makes it a partially conformationally constrained indolic phenethylamine-containing compound rather than an ergoline. UCD0179 is known to be a highly potent serotonin 5-HT2 receptor agonist similarly to LSD and to produce psychoplastogenic effects.

Structures of LSD (left) and UCD0179 (right).

Pharmacology

Pharmacodynamics

Like LSD, the drug is known to be a highly potent serotonin 5-HT2A and 5-HT2C receptor agonist in vitro. Its affinities (IC50Tooltip half-maximal inhibitory concentration) are in the ranges of 10–100 nM for the serotonin 5-HT2A receptor and 100–1,000 nM for the serotonin 5-HT2C receptor, while its activational potencies (EC50Tooltip half-maximal effective concentration) are less than 10 nM for the serotonin 5-HT2A receptor and in the range of 10–100 nM for the serotonin 5-HT2C receptor. UCD0179 was the most potent serotonin 5-HT2A receptor agonist of 27 evaluated ergoline-like compounds. In line with its serotonin 5-HT2A receptor agonism, and similarly to LSD and other psychedelics, UCD0179 has been found to produce psychoplastogenic effects on neurite growth in vitro.

Many serotonin 5-HT2A receptor agonists, for instance LSD, produce psychedelic effects in humans. The publication that reported UCD0179 specifically pertained to psychoplastogenic ergoline-like compounds with no or reduced hallucinogenic activity for potential therapeutic use. However, the hallucinogenic-related properties of UCD0179 and the other reported compounds, for instance their effects in the head-twitch response (HTR) assay, were not individually described. As such, it remains unclear whether or not UCD0179 could have psychedelic effects in humans.

Chemistry

Other related compounds in which one or more other carbons have been removed from the LSD's ergoline ring system to produce simplified and less-rigid phenethylamines and tryptamines include N-DEAOP-NMT (desvinyl-LSD) and NDTDI (9-desmethine-LSD). Desvinyl-LSD is the analogue of LSD in which the carbon atoms at positions 9 and 10 of the ergoline ring system have been removed to make a fully non-rigid tryptamine, while 9-desmethine is the analogue of LSD in which the methine at position 9 has been removed to make a rigid tricyclic tryptamine. Desvinyl-LSD has been found to produce LSD-like effects in rodents, while 9-desmethine-LSD has been encountered as a novel recreational and designer drug and made illegal in parts of Europe.

Structures of LSD (left), NDTDI (9-desmethine-LSD) (middle), and N-DEAOP-NMT (desvinyl-LSD) (right).

The analogue of UCD0179 without the ethyl groups on the amide has been described. In addition, UCD0179's analogue without the amide ethyl groups and with a phenyl ring instead of the indole ring has been described. Their activities were not reported.

"WXVL_BT0793LQ2118" chemical structure.

WXVL_BT0793LQ2118, an analogue of UCD0179 lacking the N,N-diethyl-carboxamide moiety and with a fluorine at the 6-position, has been reported. It was identified via in silico screening of 1.6 billion molecules for serotonin 5-HT2A receptor agonism with AlphaFold2. Following identification, the drug was assessed and found to be a potent serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist.

History

UCD0179 was first described in the literature by 2021. It has been patented by Delix Therapeutics.

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 WO 2021076572, Olson DE, Dunlap L, Wagner F, Chytil M, Powell NA, "Ergoline-like compounds for promoting neural plasticity", published 22 April 2021, assigned to Delix Therapeutics, Inc. and The Regents of the University of California
  2. 1 2 3 "(3R)-N,N-diethyl-5-(1H-indol-4-yl)-1-methyl-3,6-dihydro-2H-pyridine-3-carboxamide". PubChem. Retrieved 21 March 2025.
  3. ↑ Hatzipantelis CJ, Olson DE (February 2024). "The Effects of Psychedelics on Neuronal Physiology". Annu Rev Physiol. 86: 27–47. doi:10.1146/annurev-physiol-042022-020923. PMC 10922499. PMID 37931171.
  4. ↑ Vargas MV, Dunlap LE, Dong C, Carter SJ, Tombari RJ, Jami SA, et al. (February 2023). "Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors". Science. 379 (6633): 700–706. Bibcode:2023Sci...379..700V. doi:10.1126/science.adf0435. PMC 10108900. PMID 36795823.
  5. ↑ Nichols DE (October 2018). "Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)" (PDF). ACS Chem Neurosci. 9 (10): 2331–2343. doi:10.1021/acschemneuro.8b00043. PMID 29461039.
  6. ↑ Halberstadt AL (January 2015). "Recent advances in the neuropsychopharmacology of serotonergic hallucinogens". Behav Brain Res. 277: 99–120. doi:10.1016/j.bbr.2014.07.016. PMC 4642895. PMID 25036425.
  7. ↑ Kwan AC, Olson DE, Preller KH, Roth BL (November 2022). "The neural basis of psychedelic action" (PDF). Nat Neurosci. 25 (11): 1407–1419. doi:10.1038/s41593-022-01177-4. PMC 9641582. PMID 36280799.
  8. 1 2 3 4 5 6 Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085. Sklar, et al. (53) found the diethylacrylamide adduct 20 to be approximately 1/10 as active as LSD in mice, although Norris and Blicke (54) reported 21 to have little oxytocic activity. [...] 20 = R = C2H5. 21 = R = CH3 [...]
  9. 1 2 3 Norris PE, Blicke FF (December 1952). "Potential ergot substitutes: esters and amides of beta-amino acids". Journal of the American Pharmaceutical Association (Scientific Ed.). 41 (12): 637–639. doi:10.1002/jps.3030411204. PMID 13022416. Six esters and amides of derivatives of β-alanine which are related to lysergic acid have been prepared and tested for oxytocic activity. None of these products possess a significant oxytocic activity. [...] The purpose of this investigation was to synthesize amides and also esters of compounds (II–V) which represent fragments of the lysergic acid molecule in the hope that some of these products might possess oxytocic activity. Various modified fragments of the lysergic acid molecule have been synthesized previously; it was claimed that some of the compounds are active oxytocics (1—7). [...] Pharmacologic data indicated that none of the esters or amides of compounds II—V which were prepared possess a significant oxytocic action when compared to the clinically used oxytocics. However, the diethylamide of N-methyl-N-[β′-(3-indolyl)-ethyl]-β-alanine (IIIc) appeared to have an oxytocic activity approximately ten times stronger than that of the diethylamide of N-methyl-N-(β′-phenethyl)-β-alanine (IIc).
  10. 1 2 3 Analytical Report NDTDI (C19H27N3O) 3-({2-azatricyclo[6.3.1.0⁴,¹²]dodeca-1(11),3,8(12),9-tetraen-6-yl}(methyl)amino)-N,N-diethylpropanamide (PDF), European Project Response
  11. 1 2 3 Autorizēties savā kontā (March 2017). "Par aizlieguma noteikšanu vielai NDTDI un tās saturošiem izstrādājumiem" [On the prohibition of the substance NDTDI and products containing it]. LIKUMI.LV (in Latvian). Retrieved 20 March 2025.
  12. 1 2 "N,N-Diethyl-N3-methyl-N3-(1,3,4,5-tetrahydrobenzo[cd]indol-4-yl)-I(2)-alaninamide". PubChem. Retrieved 20 March 2025.
  13. 1 2 3 Julia M, Igolen J, Kolb A (20 December 1971). "Preparation de quelques phenyl et indolyl-5-tetrahydro-1.2.3.6 nicotinamides" [Preparation of some phenyl and indol-5-yl-1,2,3,6-tetrahydronicotinamides]. Comptes Rendus de l'Académie des Sciences, Série C. 273 (25): 1776–1777. Archived from the original on 2 February 2021. Alt URL
  14. 1 2 3 4 Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, et al. (March 2024). "AlphaFold2 structures template ligand discovery". bioRxiv 10.1101/2023.12.20.572662.
  15. 1 2 "6-fluoro-4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1H-indole". PubChem. Retrieved 21 March 2025.