Iboga-type alkaloid

Iboga-type alkaloids are a set of monoterpene indole alkaloids comprising naturally occurring compounds found in Tabernanthe and Tabernaemontana , as well as synthetic structural analogs. Naturally occurring iboga-type alkaloids include ibogamine, ibogaine, tabernanthine, and other substituted ibogamines (see below). Many iboga-type alkaloids display biological activities such as cardiac toxicity and psychoactive effects, and some have been studied as potential treatments for drug addiction. ^{[1] [2]}

Naturally-occurring

• 
  Ibogaine
• 
  Ibogamine
• 
  Tabernanthine
• 
  Coronaridine

Substituted ibogamines

Main article: Ibogamine

PubChem CID	Name	R1	R2	R3	R4
100217	Ibogamine	H	H	H	H
197060	Ibogaine	OMe	H	H	H
3083548	Noribogaine	OH	H	H	H
6326116	Tabernanthine	H	OMe	H	H
193302	Ibogaline	OMe	OMe	H	H
73489	Coronaridine	H	H	CO2Me	H
73255	Voacangine	OMe	H	CO2Me	H
363281	Isovoacangine	H	OMe	CO2Me	H
65572	Conopharyngine	OMe	OMe	CO2Me	H
11077316	19(S)-Hydroxyibogamine	H	H	H	OH
71656190	Iboxygaine / Kimvuline	OMe	H	H	OH
ND	ND	H	OMe	H	OH
ND	ND	OMe	OMe	H	OH
15559732	19(S)-Hydroxycoronaridine	H	H	CO2Me	OH
196982	Voacristine	OMe	H	CO2Me	OH
10362598	Isovoacristine	H	OMe	CO2Me	OH
102004638	19(S)-Hydroxyconopharyngine	OMe	OMe	CO2Me	OH

Catharanthine is an unsaturated analog of coronaridine.

Oxidation products

Similarly to other ring-constrained tryptamines such as yohimbine ^[3] and mitragynine (see mitragynine pseudoindoxyl), oxidation and rearrangement products of substituted ibogamines have been reported, such as iboluteine (ibogaine pseudoindoxyl) (CID:21589055) and voaluteine (CID:633439). ^[4]

Iboluteine (left) and voaluteine (right), putative metabolites of ibogaine and voacangine, respectively.

Other alkaloids

• Vobasine
• Ervaticine
• Dregamine
• Vinblastine

Treatment of drug dependence

Ibogaine and related alkaloids reduce the craving for subsequent doses in individuals experiencing withdrawal symptoms associated with drug addiction. Their use has been investigated in several clinical studies involving individuals dependent on opioids, cocaine, and other substances. While positive effects—such as alleviation of withdrawal symptoms, improvement in depression, and mitigation of post-traumatic symptoms—have been confirmed, severe medical complications, including fatal cases, have also been reported due to neurotoxic and cardiotoxic side effects. ^[5]

Synthetic analogues

18-MC, ME-18-MC, and 18-MAC are coronaridine analogs with similar anti-addictive effects. ^{[6] [7] [8] [9]}

More distantly related synthetic analogs include:

• Varenicline, a polycyclic azepine and anti-addictive agent that similarly targets nicotinic acetylcholine receptors, but acts as a partial agonist instead.
• Tabernanthalog is a structural simplification of tabernanthine and "non-hallucinogenic psychoplastogen". ^[10]

See also

• Strictosidine
• Bwiti
• Ibogalog
• Substituted β-carboline and harmala alkaloid

References

1. Glick, S. D.; Kuehne, M. E.; Raucci, J.; Wilson, T. E.; Larson, D.; Keller, R. W.; Carlson, J. N. (1994-09-19). "Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum" . Brain Research. 657 (1): 14–22. doi:10.1016/0006-8993(94)90948-2. ISSN   0006-8993. PMID   7820611. S2CID   1940631. Archived from the original on 2023-08-06. Retrieved 2023-08-06.
2. Antonio, Tamara; Childers, Steven R.; Rothman, Richard B.; Dersch, Christina M.; King, Christine; Kuehne, Martin; Bornmann, William G.; Eshleman, Amy J.; Janowsky, Aaron; Simon, Eric R.; Reith, Maarten E. A.; Alper, Kenneth (2013-10-16). "Effect of Iboga Alkaloids on µ-Opioid Receptor-Coupled G Protein Activation". PLOS ONE. 8 (10): e77262. Bibcode:2013PLoSO...877262A. doi: 10.1371/journal.pone.0077262 . ISSN   1932-6203. PMC   3818563 . PMID   24204784.
3. Finch, Neville; Gemenden, C. W.; Hsu, Iva Hsiu-Chu; Kerr, Ann; Sim, G. A.; Taylor, W. I. (May 1965). "Oxidative Transformations of Indole Alkaloids. III. Pseudoindoxyls from Yohimbinoid Alkaloids and Their Conversion to "Invert" Alkaloids 1,2" . Journal of the American Chemical Society. 87 (10): 2229–2235. Bibcode:1965JAChS..87.2229F. doi:10.1021/ja01088a024. ISSN   0002-7863. PMID   14290283. Archived from the original on 2023-02-07. Retrieved 2023-08-05.
4. The Alkaloids: Chemistry and Physiology V11. Academic Press. 2014-05-14. ISBN   978-0-08-086535-5. Archived from the original on 2023-08-06. Retrieved 2023-08-06.
5. Patrick Köck, Katharina Froelich, Marc Walter, Undine Lang, Kenneth M. Dürsteler (July 2022), "A systematic literature review of clinical trials and therapeutic applications of ibogaine", Journal of Substance Abuse Treatment, vol. 138, doi:10.1016/j.jsat.2021.108717, PMID   35012793 , retrieved 2022-07-05
6. Kuehne ME, He L, Jokiel PA, Pace CJ, Fleck MW, Maisonneuve IM, et al. (June 2003). "Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents". Journal of Medicinal Chemistry. 46 (13): 2716–30. doi:10.1021/jm020562o. PMID   12801235.
7. Pace CJ, Glick SD, Maisonneuve IM, He LW, Jokiel PA, Kuehne ME, Fleck MW (May 2004). "Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration". European Journal of Pharmacology. 492 (2–3): 159–67. doi:10.1016/j.ejphar.2004.03.062. PMID   15178360.
8. Glick SD, Kuehne ME, Maisonneuve IM, Bandarage UK, Molinari HH (May 1996). "18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats". Brain Research. 719 (1–2): 29–35. doi:10.1016/0006-8993(96)00056-X. PMID   8782860. S2CID   6178161.
9. Glick SD, Sell EM, Maisonneuve IM (December 2008). "Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration". European Journal of Pharmacology. 599 (1–3): 91–5. doi:10.1016/j.ejphar.2008.09.038. PMC   2600595 . PMID   18930043.
10. Cameron, Lindsay P.; Tombari, Robert J.; Lu, Ju; Pell, Alexander J.; Hurley, Zefan Q.; Ehinger, Yann; Vargas, Maxemiliano V.; McCarroll, Matthew N.; Taylor, Jack C.; Myers-Turnbull, Douglas; Liu, Taohui; Yaghoobi, Bianca; Laskowski, Lauren J.; Anderson, Emilie I.; Zhang, Guoliang (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. ISSN   1476-4687. PMC   7874389 . PMID   33299186.