DEIMDHPCA

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| image = 11 from WO 2021-076572 structure.png

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| class = Serotonin 5-HT₂ receptor agonist; Psychoplastogen; Simplified/partial LSD analogue

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| CAS_number = 2640392-28-3

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| PubChem = 156278040

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| synonyms = "Compound 11"

| IUPAC_name = (3R)-N,N-diethyl-5-(1H-indol-4-yl)-1-methyl-3,6-dihydro-2H-pyridine-3-carboxamide

| C=19 | H=25 | N=3 | O=1

| SMILES = CCN(CC)C(=O)[C@H]1CN(CC(=C1)C2=C3C=CNC3=CC=C2)C

| StdInChI = 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

| StdInChIKey = GDCMLRPQENDWLG-OAHLLOKOSA-N

}}

DEIMDHPCA is an indole derivative and a "partial" or simplified ergoline which is closely related to the highly potent serotonergic psychedelic lysergic acid diethylamide (LSD).{{cite patent | country = WO | number = 2021076572 | inventor = Olson DE, Dunlap L, Wagner F, Chytil M, Powell NA | status = | title = Ergoline-like compounds for promoting neural plasticity | pubdate = 22 April 2021 | gdate = | fdate = 14 October 2020 | pridate = 14 October 2020 | assign1 = Delix Therapeutics, Inc. | assign2 = The Regents of the University of California | url =https://patents.google.com/patent/WO2021076572/ }}{{cite web | title=(3R)-N,N-diethyl-5-(1H-indol-4-yl)-1-methyl-3,6-dihydro-2H-pyridine-3-carboxamide | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/156278040 | access-date=21 March 2025}} 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 DEIMDHPCA molecule more flexible and makes it a partially rigid indolic phenethylamine-containing compound rather than an ergoline. DEIMDHPCA is known to be a highly potent serotonin 5-HT₂ receptor agonist similarly to LSD and to produce psychoplastogenic effects.

File:LSD and DEIMDHPCA chemical structures.png (left) and DEIMDHPCA (right) chemical structures.]]

Pharmacology

Like LSD, the drug is known to be a highly potent serotonin 5-HT_2A and 5-HT_2C receptor agonist in vitro. Its affinities ({{Abbrlink|IC₅₀|half-maximal inhibitory concentration}}) are in the ranges of 10–100{{nbsp}}nM for the serotonin 5-HT_2A receptor and 100–1,000{{nbsp}}nM for the serotonin 5-HT_2C receptor, while its activational potencies ({{Abbrlink|EC₅₀|half-maximal effective concentration}}) are less than 10{{nbsp}}nM for the serotonin 5-HT_2A receptor and in the range of 10–100{{nbsp}}nM for the serotonin 5-HT_2C receptor. DEIMDHPCA was the most potent serotonin 5-HT_2A receptor agonist of 27{{nbsp}}evaluated ergoline-like compounds. In line with its serotonin 5-HT_2A receptor agonism, and similarly to LSD and other psychedelics,{{cite journal | vauthors = Hatzipantelis CJ, Olson DE | title = The Effects of Psychedelics on Neuronal Physiology | journal = Annu Rev Physiol | volume = 86 | issue = | pages = 27–47 | date = February 2024 | pmid = 37931171 | pmc = 10922499 | doi = 10.1146/annurev-physiol-042022-020923 | url = }}{{cite journal | vauthors = Vargas MV, Dunlap LE, Dong C, Carter SJ, Tombari RJ, Jami SA, Cameron LP, Patel SD, Hennessey JJ, Saeger HN, McCorvy JD, Gray JA, Tian L, Olson DE | title = Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors | journal = Science | volume = 379 | issue = 6633 | pages = 700–706 | date = February 2023 | pmid = 36795823 | pmc = 10108900 | doi = 10.1126/science.adf0435 | bibcode = 2023Sci...379..700V | url = }} DEIMDHPCA has been found to produce psychoplastogenic effects on neurite growth in vitro.

Many serotonin 5-HT_2A receptor agonists, for instance LSD, produce psychedelic effects in humans.{{cite journal | vauthors = Nichols DE | title = Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD) | journal = ACS Chem Neurosci | volume = 9 | issue = 10 | pages = 2331–2343 | date = October 2018 | pmid = 29461039 | doi = 10.1021/acschemneuro.8b00043 | url = https://shaunlacob.com/wp-content/uploads/2020/12/DC-LSD.pdf}}{{cite journal | vauthors = Halberstadt AL | title = Recent advances in the neuropsychopharmacology of serotonergic hallucinogens | journal = Behav Brain Res | volume = 277 | issue = | pages = 99–120 | date = January 2015 | pmid = 25036425 | doi = 10.1016/j.bbr.2014.07.016 | url = | pmc = 4642895 }}{{cite journal | vauthors = Kwan AC, Olson DE, Preller KH, Roth BL | title = The neural basis of psychedelic action | journal = Nat Neurosci | volume = 25 | issue = 11 | pages = 1407–1419 | date = November 2022 | pmid = 36280799 | pmc = 9641582 | doi = 10.1038/s41593-022-01177-4 | url = https://alexkwanlab.org/wp-content/uploads/2022/11/kwanNatNeurosci2022.pdf}} The publication that reported DEIMDHPCA specifically pertained to psychoplastogenic ergoline-like compounds with no or reduced hallucinogenic activity for potential therapeutic use. However, the hallucinogenic-related properties of DEIMDHPCA 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 DEIMDHPCA could have psychedelic effects in humans.

History

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

Related compounds

File:LSD, NDTDI, and N-DEAOP-NMT chemical structures.png (left), NDTDI (center), and N-DEAOP-NMT (right) chemical structures.]]

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{{cite thesis | vauthors = Nichols DE | title = Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid | date = May 1973 | publisher = University of Iowa | pages = 23 | oclc = 1194694085 | url = https://bitnest.netfirms.com/external/Theses/Nichols1973#page=32 | quote = 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 [...]}}{{cite journal | vauthors = Norris PE, Blicke FF | title = Potential ergot substitutes: esters and amides of beta-amino acids | journal = J Am Pharm Assoc Am Pharm Assoc | volume = 41 | issue = 12 | pages = 637–639 | date = December 1952 | pmid = 13022416 | doi = 10.1002/jps.3030411204 | url = | quote = 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).}} and NDTDI.{{citation | title = 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 | publisher = European Project Response | url = https://www.policija.si/apps/nfl_response_web/0_Analytical_Reports_final/NDTDI-ID-1737-16_report.pdf}}{{cite web | author=Autorizēties savā kontā | title=Par aizlieguma noteikšanu vielai NDTDI un tās saturošiem izstrādājumiem | trans-title=On the prohibition of the substance NDTDI and products containing it | website=LIKUMI.LV | date=March 2017 | url=https://likumi.lv/ta/id/289200 | language=lv | access-date=20 March 2025}}{{cite web | title=N,N-Diethyl-N3-methyl-N3-(1,3,4,5-tetrahydrobenzo[cd]indol-4-yl)-I(2)-alaninamide | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/163192742 | access-date=20 March 2025}} N-DEAOP-NMT 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 NDTDI is the analogue of LSD in which only the carbon at position 9 has been removed to make a rigid tricyclic tryptamine. N-DEAOP-NMT has been found to produce LSD-like effects in rodents, while NDTDI has been encountered as a novel recreational and designer drug and made illegal in parts of Europe.

The analogue of DEIMDHPCA without the ethyl groups on the amide has been described.{{cite journal | vauthors = Julia M, Igolen J, Kolb A | title = Preparation de quelques phenyl et indolyl-5-tetrahydro-1.2.3.6 nicotinamides | trans-title = Preparation of some phenyl and indol-5-yl-1,2,3,6-tetrahydronicotinamides | journal = Comptes rendus hebdomadaires des séances de l'Académie des sciences. Série C | date = 20 December 1971 | volume = 273 | issue = 25 | pages = 1776–1777 | url = https://scholar.google.com/scholar?q=%22PREPARATION+OF+SOME+PHENYL+AND+INDOL-5-YL+1%2C+2%2C+3%2C+6-TETRAHYDRONICOTINAMIDES%22 | archive-url = https://archive.org/details/cr-268/CR_273/page/1776/mode/1up | archive-date = 2 February 2021}} In addition, DEIMDHPCA'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.

File:WXVL BT0793LQ2118 structure.png.]]

WXVL_BT0793LQ2118, an analogue of DEIMDHPCA lacking the N,N-diethyl-carboxamide moiety and with a fluorine at the 6-position, has been reported.{{cite journal | vauthors = Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, Barros-Álvarez X, Sakamoto K, Kim Y, DiBerto J, Kim K, Tummino TA, Huang S, Irwin JJ, Tarkhanova OO, Moroz Y, Skiniotis G, Kruse AC, Shoichet BK, Roth BL | title = AlphaFold2 structures template ligand discovery | journal = bioRxiv | volume = | issue = | pages = | date = March 2024 | pmid = 38187536 | pmc = 10769324 | doi = 10.1101/2023.12.20.572662 | url = }}{{cite web | title=6-fluoro-4-(1-methyl-3,6-dihydro-2H-pyridin-5-yl)-1H-indole | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/171676435 | access-date=21 March 2025}} It was identified via in silico screening of 1.6{{nbsp}}billion molecules for serotonin 5-HT_2A receptor agonism with AlphaFold2. Following identification, the drug was assessed and found to be a potent serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptor agonist.