Class of chemical compounds
Chemical structure oftabernanthalog (TBG; DLX-007), one of the most well-known ibogalogs.[ 1] Anibogalog , orsimplified ibogaine analogue , also known as asubstituted 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (or simplysubstituted hexahydroazepinoindole ), is aderivative ofnoribogaminalog and a simplifiedanalogue ofiboga alkaloids and related compounds such asibogaine .[ 1] [ 2] [ 3] [ 4] tricyclic cyclized tryptamines and are closely related to theβ-carbolines orharmala alkaloids .[ 1] [ 2] [ 4] hydrogenated 7-memberedazepine ring instead of the variably-saturated 6-memberedpyridine ring present in β-carbolines.[ 1] [ 2] indole and hydrogenated azepine rings, but theisoquinuclidine (2-azabicyclo[2.2.2]octane)ring system has been removed, simplifying thechemical structure .[ 1] [ 4]
Ibogalogs have been limitedly tested in humans, butanecdotal reports concerningtabernanthalog exist.[ 5] [ 6] [ 7]
Ibogalogs are known to act aspotent serotonin 5-HT2A and5-HT2C receptor agonists , as well as acting as agonists of otherserotonin receptors .[ 2] [ 4] [ 8] iboga alkaloids likeibogaine andnoribogaine , which are inactive asserotonin receptor agonists .[ 1] 5-HT2B receptor antagonism orpartial agonism ,[ 2] monoamine reuptake inhibition ,[ 2] nicotinic acetylcholine receptor inhibition .[ 9] [ 10] opioid receptor agonism, for instance of theκ-opioid receptor .[ 1] potency at thehERG antitarget compared to ibogaine, which confers much lesscardiotoxicity .[ 1] [ 4]
Ibogalogs have been reported to producepsychoplastogenic ,[ 2] [ 1] antidepressant -like,[ 2] [ 1] anxiolytic -like,[ 11] sedative -like,[ 11] [ 12] antiaddictive -like,[ 1] [ 13] analgesic effects in animals.[ 14] [ 15] head-twitch response , a behavioral proxy ofserotonergic psychedelic activity,ibogainalog may produce psychedelic effects in humans, while other assessed ibogainalogs, includingtabernanthalog ,ibogaminalog ,noribogainalog , andcatharanthalog , appear to be non-psychedelic.[ 1] [ 11] [ 15] [ 4] PNU-22394 was non-hallucinogenic inclinical studies .[ 8]
Ibogalogs, such asPNU-22394 , were first developed and described in the 1960s.[ 12] [ 16] appetite suppressants andweight loss drugs .[ 17] [ 8] [ 18] David E. Olson and colleagues at theUniversity of California, Davis andDelix Therapeutics , as potential treatments ofcentral nervous system disorders .[ 19] [ 1] [ 2] tabernanthalog (TBG; DLX-007) is under development for potential medical use.[ 1] [ 20] [ 21]
Structure Name Synonyms Chemical name Iboga analogue Ref Noribogaminalog 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole Noribogamine [ 16] Ibogaminalog DM-506 3-methyl-2,4,5,6-tetrahydro-1H -azepino[4,5-b]indole Ibogamine Noribogainalog Nor-IBG 9-hydroxy-3-methyl-2,4,5,6-tetrahydro-1H -azepino[4,5-b]indole Noribogaine Ibogainalog IBG 9-methoxy-3-methyl-2,4,5,6-tetrahydro-1H -azepino[4,5-b]indole Ibogaine [ 1] Tabernanthalog TBG; DLX-007 8-methoxy-3-methyl-2,4,5,6-tetrahydro-1H -azepino[4,5-b]indole Tabernanthine [ 1] Catharanthalog CAG methyl 3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate Catharanthine [ 22] [ 15] Fluorogainalog 9-fluoro-3-methyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole [ 23] [ 24] LS-22925 9-fluoro-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole [ 25] PNU-22394 U-22394 6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole [ 17] [ 18]
Structure Name Synonyms Chemical name Ref PHA-57378 2,7,8,9,10,11-hexahydro-1H -azepino[4,5-b][1,4]oxazino[2,3,4-hi]indole PNU-181731 2,3,4,5-tetrahydro-1H -[1,4]diazepino[1,7-a]indole
^a b c d e f g h i j k l m n o p Cameron LP, Tombari RJ, Lu J, Pell AJ, Hurley ZQ, Ehinger Y, Vargas MV, McCarroll MN, Taylor JC, Myers-Turnbull D, Liu T, Yaghoobi B, Laskowski LJ, Anderson EI, Zhang G, Viswanathan J, Brown BM, Tjia M, Dunlap LE, Rabow ZT, Fiehn O, Wulff H, McCorvy JD, Lein PJ, Kokel D, Ron D, Peters J, Zuo Y, Olson DE (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 . ^a b c d e f g h i Arias HR, Rudin D, Luethi D, Valenta J, Leśniak A, Czartoryska Z, Olejarz-Maciej A, Doroz-Płonka A, Manetti D, De Deurwaerdère P, Romanelli MN, Handzlik J, Liechti ME, Chagraoui A (January 2025)."The psychoplastogens ibogaminalog and ibogainalog induce antidepressant-like activity in naïve and depressed mice by mechanisms involving 5-HT2A receptor activation and serotonergic transmission" .Prog Neuropsychopharmacol Biol Psychiatry .136 111217.doi :10.1016/j.pnpbp.2024.111217 PMID 39662723 . ^ Iyer RN, Favela D, Zhang G, Olson DE (March 2021)."The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs" .Nat Prod Rep .38 (2):307– 329.doi :10.1039/d0np00033g .PMC 7882011 PMID 32794540 . ^a b c d e f Zięba A, Stępnicki P, Matosiuk D, Kaczor AA (December 2021)."Overcoming Depression with 5-HT2A Receptor Ligands" .International Journal of Molecular Sciences .23 (1): 10.doi :10.3390/ijms23010010 PMC 8744644 PMID 35008436 . ^ Love, Shayla (20 October 2024)."Tripping on Nothing" .The Atlantic . Archived fromthe original on 8 February 2025. ^ Hardman, Josh (19 July 2023)."Non-Hallucinogenic Trip Reports: Searching for the Tabernanthalog Tasters" .Psychedelic Alpha . Retrieved14 October 2025 . ^ Juliani, Arthur (30 December 2023)."A Phenomenological Report on the Novel Non-Hallucinogenic Psychedelic Tabernanthalog" .Medium . Retrieved14 October 2025 . ^a b c Fitzgerald, Lawrence W; Ennis, Michael D (2002). "Chapter 3: 5-HT2C receptor modulators: Progress in development of new CNS medicines".Annual Reports in Medicinal Chemistry . Vol. 37. Elsevier. pp. 21– 30.doi :10.1016/s0065-7743(02)37004-0 .ISBN 978-0-12-040537-4 The closely related azepinoindole 11 (PNU-22394) has been described as a 5-HT2C agonist (Ki = 18.8 nM, 83% efficacy) that has recently been reported to decrease feeding in rats and produce a weight loss in humans (68). Although dose-related clinical side effects observed included headache, anxiety, nausea, and vomiting, these effects were dramatically reduced following four days of dosing. No hallucinations were observed despite the fact that 11 is also a potent, high efficacy 5-HT2A agonist (5-HT2A Ki = 19 nM, 64% efficacy). Compound 11 also has excellent affinity at 5-HT2B receptors (Ki = 28.5 nM). ^ Tae, Han-Shen; Ortells, Marcelo O.; Tekarli, Bassel J.; Manetti, Dina; Romanelli, Maria Novella; McIntosh, J. Michael; Adams, David J.; Arias, Hugo R. (19 July 2023)."DM506 (3-Methyl-1,2,3,4,5,6-hexahydroazepino[4,5- b ]indole fumarate), a Novel Derivative of Ibogamine, Inhibits α7 and α9α10 Nicotinic Acetylcholine Receptors by Different Allosteric Mechanisms" ACS Chemical Neuroscience .14 (14):2537– 2547.doi :10.1021/acschemneuro.3c00212 .ISSN 1948-7193 .PMID 37386821 . Retrieved28 July 2025 . ^ Tae HS, Ortells MO, Yousuf A, Xu SQ, Akk G, Adams DJ, Arias HR (May 2024)."Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABAA receptor and CaV2.2 channel" .Biochem Pharmacol .223 116183.doi :10.1016/j.bcp.2024.116183 .PMC 11151864 PMID 38580167 . ^a b c Arias, Hugo R.; Rudin, Deborah; Hines, Dustin J.; Contreras, April; Gulsevin, Alican; Manetti, Dina; Anouar, Youssef; De Deurwaerdere, Philippe; Meiler, Jens; Romanelli, Maria Novella; Liechti, Matthias E.; Chagraoui, Abdeslam (2024)."The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT2A receptor activation" (PDF) .European Journal of Pharmacology .966 176329.doi :10.1016/j.ejphar.2024.176329 PMID 38253116 . Retrieved28 July 2025 . ^a b Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds".Hallucinogenic Agents 98– 144.ISBN 978-0-85608-011-1 OCLC 2176880 .OL 4850660M .The iboga alkaloids are long overdue for a detailed examination of their psychic effects in man. It is interesting that simplification of the iboga structure to give the hexahydroazepino[4,5-b]indoles (for example, 4.42) enhances the tryptamine-like properties, at least as far as tremorogenic activity is concerned, but also enhances the sedative effects. Thus, these compounds have chlorpromazine-like properties in both man and animals (Hester, Tang, Keesling, and Veldkamp, 1968). ^ Heinsbroek JA, Giannotti G, Bonilla J, Olson DE, Peters J (June 2023)."Tabernanthalog Reduces Motivation for Heroin and Alcohol in a Polydrug Use Model" .Psychedelic Med (New Rochelle) .1 (2):111– 119.doi :10.1089/psymed.2023.0009 .PMC 10286262 PMID 37360328 . ^ Arias HR, Micheli L, Rudin D, Bento O, Borsdorf S, Ciampi C, Marin P, Ponimaskin E, Manetti D, Romanelli MN, Ghelardini C, Liechti ME, Di Cesare Mannelli L (August 2024). "Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT2A receptor activation".Biomed Pharmacother .177 116867.doi :10.1016/j.biopha.2024.116867 .hdl :2158/1371514 PMID 38889634 . ^a b c Arias HR, Micheli L, Jensen AA, Galant S, Vandermoere F, Venturi D, Manetti D, Romanelli MN, Ghelardini C, Marin P, Di Cesare Mannelli L (March 2025). "Ibogalogs decrease neuropathic pain in mice through a mechanism involving crosstalk between 5-HT2A and mGlu2 receptors".Biomed Pharmacother .184 117887.doi :10.1016/j.biopha.2025.117887 .hdl :2158/1423286 PMID 39938347 . ^a b Hester JB, Tang AH, Keasling HH, Veldkamp W (January 1968). "Azepinoindoles. I. Hexahydroazepino[4,5-b]indoles".J Med Chem .11 (1):101– 106.doi :10.1021/jm00307a023 .PMID 5637151 . ^a b McCall, R. B., Franklin, S. R., Hyslop, D. K., Knauer, C. S., Chio, C. L., Haber, C. L., & Fitzgerald, L. W. (2001). PNU-22394, a 5-HT2C receptor agonist, reduces feeding in rodents and produces weight loss in humans. In Soc Neurosci Abstr (Vol. 27, No. 309.2).https://scholar.google.com/scholar?cluster=17067737110870651783 ^a b Bishop, Michael J; Nilsson, Björn M (2003)."New 5-HT2C receptor agonists" Expert Opinion on Therapeutic Patents .13 (11):1691– 1705.doi :10.1517/13543776.13.11.1691 .ISSN 1354-3776 . Retrieved28 July 2025 . ^ Extance, Andy; Extance, Andy; McVean, Ada; Robinson, Julia; Welter, Kira; Durrani, Jamie; Extance, Andy (17 December 2020)."Chemists tame shamanic addiction treatment" .Chemistry World . Retrieved28 July 2025 . ^ "DLX 7" .AdisInsight . 20 February 2023. Retrieved18 November 2024 .^ "Delving into the Latest Updates on DLX-7 with Synapse" .Synapse . 7 November 2024. Retrieved18 November 2024 .^ "Methyl 3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate" .PubChem . Retrieved28 July 2025 .^ "9-fluoro-3-methyl-2,4,5,6-tetrahydro-1H-azepino[4,5-b]indole" .PubChem . Retrieved28 July 2025 .^ Sutton C, Williams EQ, Homsi H, Beerepoot P, Nazari R, Han D, Ramsey AJ, Mash DC, Olson DE, Blough B, Salahpour A (2022)."Structure-Activity Relationships of Dopamine Transporter Pharmacological Chaperones" .Front Cell Neurosci .16 832536.doi :10.3389/fncel.2022.832536 PMC 9124866 PMID 35614973 . ^ "9-Fluoro-1,2,3,4,5,6-hexahydro-azepino(4,5-b)indole" .PubChem . 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Tryptamines 4-Hydroxytryptamines esters /ethers 5-Hydroxy- and5-methoxytryptamines 2-Methyl-5-HT 4-HO-5-MeO-T 4-F-5-MeO-DMT 4,5-DHP-DMT 4,5-DHT 4,5-MDO-DMT 4,5-MDO-DiPT 5-BT 5-Ethoxy-DMT 5-HO-DET 5-HO-DiPT 5-HO-NiPT 5-HO-DPT 5-HTP (oxitriptan )5-MeO-2-TMT 5-MeO-34MPEMT 5-MeO-7,N ,N -TMT 5-MeO-DALT 5-MeO-DBT 5-MeO-DET 5-MeO-DiPT 5-MeO-DMT (N ,N ,O -TMS;O -methylbufotenine) 5-MeO-DPT 5-MeO-EiPT 5-MeO-EPT 5-MeO-MALT 5-MeO-MET 5-MeO-MiPT 5-MeO-NET 5-MeO-NiPT 5-MeO-NMT (O ,N -DMS) 5-MeO-PiPT 5-MeO-NBpBrT 5-MeO-T (5-MT; mexamine;O -methylserotonin) 5-MeO-T-NBOMe 5-MT-NB3OMe 5-NOT 5,6-DHT 5,6-MDO-DiPT 5,6-MDO-DMT 5,6-MDO-MiPT 5,6-MeO-MiPT 5,7-DHT Arachidonoyl serotonin ASR-3001 (5-MeO-iPALT) BAB Benanserin (BAS; SQ-4788) BGC20-761 Bufotenidine (5-HTQ;N ,N ,N -TMS) Bufotenin (5-HO-DMT;N ,N -DMS; mappine) Bufoviridine (5-SO-DMT) CP-132,484 Cqd 280 Cqd 285 Cqdd 280 Donitriptan EMDT (2-Et-5-MeO-DMT) HIOC Indorenate (TR-3369) Isamide (N -CA-5-MT) L-741604 MS-245 N -DEAOP-5-MeO-NETN -DEAOP-5-MeO-NMTN -Feruloylserotonin (moschamine)Norbufotenin (5-HO-NMT; NMS) O -Acetylbufotenine (5-AcO-DMT)O -Pivalylbufotenine (5-t -BuCO-DMT)Psilomethoxin (4-HO-5-MeO-DMT) Psilomethoxybin (4-PO-5-MeO-DMT) Serotonin (5-HT) N -Acetyltryptaminesα-Alkyltryptamines 5-Hydroxy- and 5-alkoxy-α-alkyltryptamines: 1-Pr-5-MeO-AMT 5-Allyloxy-AMT 5-Ethoxy-αMT 5-iPrO-αMT 5-MeO-αET 5-MeO-αMT (α,O -DMS; Alpha-O) α-Methyl-5-HTP α-Methylmelatonin α-Methylserotonin (5-HO-αMT; α-Me-5-HT) α,N ,O -TMS (5-MeO-α,N -DMT) α,N ,N ,O -TeMS (5-MeO-α,N ,N -TMT) AL-37350A (4,5-DHP-αMT) BW-723C86 Cyclized tryptamines Barettin Cyclic 3-OHM Ergolines andlysergamides (e.g.,LSD )Harmala alkaloidsβ-carbolines (e.g.,5-methoxyharmalan ,6-MeO-THH ,6-methoxyharmalan ,9-Me-BC ,β-carboline (norharman) ,fenharmane ,harmaline ,harmalol ,harmane ,harmine ,LY-266,097 ,pinoline ,tetrahydroharmine ,tryptoline )Iboga alkaloidsibogaine ,ibogamine ,noribogaine ,tabernanthine )Ibogalogs (e.g.,catharanthalog ,fluorogainalog ,ibogainalog ,ibogaminalog (DM-506) ,LS-22925 ,noribogainalog ,noribogaminalog ,PHA-57378 ,PNU-22394 ,tabernanthalog )Imidazolylindoles (e.g.,AGH-107 ,AGH-192 ,AH-494 )Metralindole Partial ergolines and lysergamides (e.g.,NDTDI ,RU-27849 ,RU-28251 ,RU-28306 ,FHATHBIN ,LY-178210 ,Bay R 1531 (LY-197206) ,LY-293284 ,10,11-seco-LSD ,10,11-secoergoline (α,N -Pip-T) ,CT-5252 )Pertines (e.g.,alpertine ,milipertine ,oxypertine ,solypertine )Piperidinylethylindoles (e.g.,pip-T ,indolylethylfentanyl )Pyrrolidinylethylindoles (e.g.,pyr-T ,4-HO-pyr-T ,5-MeO-pyr-T ,4-F-5-MeO-pyr-T )Pyrrolidinylmethylindoles (e.g.,MPMI ,4-HO-MPMI (lucigenol) ,5F-MPMI ,5-MeO-MPMI ,CP-122288 ,CP-135807 ,eletriptan )Tetrahydrocarbazolamines (e.g.,ciclindole ,flucindole ,frovatriptan ,LY-344864 ,ramatroban )Tetrahydropyridinylindoles (e.g.,RS134-49 ,RU-28253 ,NEtPhOH-THPI )Tetrahydropyrroloquinolines (e.g.,bufothionine ,O -methylnordehydrobufotenineYohimbans (e.g.,yohimbine ,rauwolscine ,spegatrine ,corynanthine ,ajmalicine ,reserpine ,deserpidine ,rescinnamine )Isotryptamines Related compounds 2-Azapsilocin 4-Aza-5-MeO-DPT 5-Aza-4-MeO-DiPT 5-HIAA 5-HIAL 5-HITCA 5-MIAL 7-Aza-5-MeO-DiPT α-Carboline γ-Carbolines (pyridoindoles) (e.g.,γ-carboline ,alosetron ,gevotroline ,latrepirdine ,lurosetron ,mebhydrolin ,tiflucarbine )Amedalin Benzindopyrine Benzofurans (e.g.,3-APB ,5-MeO-DiBF ,BPAP ,3-F-BPAP ,dimemebfe ,mebfap ,oxa-noribogaine )Benzothiophenes (e.g.,3-APBT )Carmoxirole CT-4436 Daledalin Gramine Histamine I-32 IAL IN-399 Indazolethylamines (e.g.,AL-34662 ,AL-38022A ,O -methyl-AL-34662VU6067416 ,YM-348 )Indenylethylamines (e.g.,C-DMT )Indolizinylethylamines (e.g.,TACT908 (2ZEDMA) ,1ZP2MA ,1Z2MAP1O )Indolylaminopropanes (e.g.,1-API ,2-API ,4-API ,5-API (5-IT; PAL-571) ,6-API (6-IT) ,7-API )Iprindole Masupirdine Medmain Molindone Non-tryptaminetriptans (e.g.,avitriptan ,LY-334370 ,naratriptan ) Ondansetron Oxazinopyridoindoles (e.g.,IHCH-8134 )Phenethylamines (e.g.,phenethylamine ,amphetamine )Piperidinylbenzimidazolines (e.g.,benperidol ,timiperone )Piperazinylbenzisothiazoles (e.g.,lurasidone ,perospirone ,tiospirone ,ziprasidone )Piperidinylbenzisoxazoles (e.g.,iloperidone ,milsaperidone ,ocaperidone ,paliperidone ,risperidone )Piperidinylindoles (e.g.,BRL-54443 ,LY-334370 ,naratriptan ,sertindole ,SN-22 )Pirlindole Pyridinylbenzimidazoles (e.g.,droperidol )Pyridinylindoles (e.g.,tepirindole )Pyridopyrroloquinoxalines (e.g.,IHCH-7113 ,IHCH-7079 ,IHCH-7086 ,lumateperone ,deulumateperone ,ITI-1549 )Pyrrolylethylamines (e.g.,2-pyrrolylethylamine (NEA) ,3-pyrrolylethylamine (3-NEA) ,3-pyrrolylpropylamine )Pyrrolopyridinylethylamines (e.g.,WAY-208466 )Quinolinylethylamines (e.g.,mefloquine )Ro60-0213 Selisistat Tetrahydropyridinylindoles (e.g.,EMD-386088 ,LY-367265 ,RU-24,969 )Tetrahydropyridinylpyrrolopyridines (e.g.,(R )-69 (3IQ) ,(R )-70 ,CP-94253 )Tetrindole Tipindole Zilpaterol (RU-42173)
