Chemistry:Ibogainalog
Ibogainalog (IBG), also known as 9-methoxyibogaminalog, is a non-selective serotonin receptor modulator, serotonergic psychedelic, and psychoplastogen of the ibogalog group related to the iboga alkaloid ibogaine but with a simplified chemical structure.[1][2][3]
Pharmacology
Pharmacodynamics
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | ND (Ki) 6,911 (EC50) 91% (Emax) |
| 5-HT1B | ND (Ki) 170 (EC50) 76% (Emax) |
| 5-HT1D | ND (Ki) 6,043 (EC50) 82% (Emax) |
| 5-HT1E | ND (Ki) 9,309 (EC50) 126% (Emax) |
| 5-HT1F | ND (Ki) 35 (EC50) 85% (Emax) |
| 5-HT2A | 670 (Ki) 18–85 (EC50) 55–93% (Emax) |
| 5-HT2B | 169 (Ki) 11,130 or IA (EC50) 58% or IA (Emax) |
| 5-HT2C | 810 (Ki) 4.0–19 (EC50) 13–97% (Emax) |
| 5-HT3 | ND |
| 5-HT4 | ND (Ki) >10,000 (EC50) |
| 5-HT5A | ND (Ki) >10,000 (EC50) |
| 5-HT6 | ND (Ki) 7.1–8.8 (EC50) 83–99% (Emax) |
| 5-HT7 | ND (Ki) 335 (EC50) –17% (Emax) |
| α1A–α1D | ND |
| α2A–α2C | ND |
| β1–β3 | ND |
| D1–D5 | ND |
| H1–H4 | ND |
| M1–M5 | ND |
| nACh | ND |
| I1, I2 | ND |
| σ1, σ2 | ND |
| MOR | ND (Ki) IA (EC50) |
| DOR | ND (Ki) IA (EC50) |
| KOR | ND (Ki) >10,000 (EC50) |
| NMDAR | ND |
| TAAR1 | ND |
| SERT | ND (Ki) 400 (IC50) |
| NET | ND (Ki) 20,000 (IC50) |
| DAT | ND (Ki) 246,000 (IC50) |
| MAO-A | 39% FI @ 100 μM |
| MAO-B | 0% FI @ 100 μM |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [3][4][5][6] | |
Ibogainalog acts as a non-selective serotonin receptor modulator, including as an agonist of the serotonin 5-HT1B, 5-HT1F, 5-HT2A, and 5-HT6 receptors, as an agonist or antagonist of the serotonin 5-HT2B and 5-HT2C receptors, and as an inverse agonist of the serotonin 5-HT7 receptor.[3][4][5][6] Unlike noribogaine, IBG shows no activation of the opioid receptors or κ-opioid receptor agonism.[3] In addition to its actions at serotonin receptors, IBG weakly inhibits certain nicotinic acetylcholine receptors.[7] The drug also acts as a relatively weak serotonin reuptake inhibitor.[5]
The drug produces the head-twitch response in animals and hence shows psychedelic-like effects.[1][3] However, it has reduced and relatively weak hallucinogen-like effects compared to 5-MeO-DMT.[1][5][3] Conversely, tabernanthalog (TBG), a simplified analogue of tabernanthine and positional isomer of IBG, appears to be completely non-hallucinogenic.[1][3] IBG shows comparable psychoplastogenic activity to ibogaine.[1] In contrast to ibogaine, IBG and TBG appear to have much less or no potential for cardiotoxicity secondary to hERG inhibition.[1][3] However, TBG showed a better overall safety profile than IBG and was selected for development instead of IBG.[1][3] IBG shows analgesic effects against neuropathic pain and visceral pain in animals that appear to be mediated by serotonin 5-HT2A receptor activation.[4]
In early animal studies, ibogainalog was described as having enhanced tryptamine-like, tremorogenic, and sedative effects compared to ibogaine.[8][9] It was also said to have chlorpromazine-like effects.[8][9]
Chemistry
IBG can be viewed as a conformationally restricted analogue of 5-MeO-DMT, whereas TBG can be viewed as a conformationally restricted analogue of 6-MeO-DMT.[2][3] Owing to their simplified structures, the chemical syntheses of IBG and TBG are much more practical than the synthesis of ibogaine.[1]
History
Ibogainalog was first described in the scientific literature by 1968.[8][9] Subsequently, it was studied and described in greater detail by David E. Olson and colleagues in the 2020s.[3]
Society and culture
Legal status
Canada
Ibogainalog is not an explicitly nor implicitly controlled substance in Canada as of 2025.[10]
United States
Ibogainalog is not an explicitly controlled substance in the United States.[11] However, it could be considered a controlled substance under the Federal Analogue Act if intended for human consumption.
See also
- Ibogalog
- Ibogaine
- Catharanthalog
- Ibogaminalog (DM-506)
- Noribogainalog
- PNU-22394
- Tabernanthalog (DLX-007)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "Overcoming Depression with 5-HT2A Receptor Ligands". International Journal of Molecular Sciences 23 (1): 10. December 2021. doi:10.3390/ijms23010010. PMID 35008436.
- ↑ 2.0 2.1 "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews 124 (1): 124–163. January 2024. doi:10.1021/acs.chemrev.3c00375. PMID 38033123.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 "A non-hallucinogenic psychedelic analogue with therapeutic potential". Nature 589 (7842): 474–479. January 2021. doi:10.1038/s41586-020-3008-z. PMID 33299186. Bibcode: 2021Natur.589..474C.
- ↑ 4.0 4.1 4.2 "Non-hallucinogenic compounds derived from iboga alkaloids alleviate neuropathic and visceral pain in mice through a mechanism involving 5-HT2A receptor activation". Biomedicine & Pharmacotherapy 177. August 2024. doi:10.1016/j.biopha.2024.116867. PMID 38889634.
- ↑ 5.0 5.1 5.2 5.3 "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. January 2025. doi:10.1016/j.pnpbp.2024.111217. PMID 39662723.
- ↑ 6.0 6.1 "Ibogalogs decrease neuropathic pain in mice through a mechanism involving crosstalk between 5-HT2A and mGlu2 receptors". Biomed Pharmacother 184. March 2025. doi:10.1016/j.biopha.2025.117887. PMID 39938347.
- ↑ "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". Biochemical Pharmacology 223. May 2024. doi:10.1016/j.bcp.2024.116183. PMID 38580167.
- ↑ 8.0 8.1 8.2 "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. Retrieved 2025-06-15. "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)."
- ↑ 9.0 9.1 9.2 "Azepinoindoles. I. Hexahydroazepino[4,5-b]indoles". J Med Chem 11 (1): 101–106. January 1968. doi:10.1021/jm00307a023. PMID 5637151.
- ↑ "Controlled Drugs and Substances Act". 5 December 2025. https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html.
- ↑ Orange Book: List of Controlled Substances and Regulated Chemicals (January 2026), United States: U.S. Department of Justice: Drug Enforcement Administration (DEA): Diversion Control Division, January 2026, https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf
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