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

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	COOMe	H
73255	Voacangine	OMe	H	COOMe	H
363281	Isovoacangine	H	OMe	COOMe	H
65572	Conopharyngine	OMe	OMe	COOMe	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	COOMe	OH
196982	Voacristine	OMe	H	COOMe	OH
10362598	Isovoacristine	H	OMe	COOMe	OH
102004638	19(S)-Hydroxyconopharyngine	OMe	OMe	COOMe	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.[4]

Other alkaloids

• Vobasine
• Ervaticine
• Dregamine
• Vinblastine

Synthetic analogs

18-MC, ME-18-MC, and 18-MAC are coronaridine analogs with similar anti-addictive effects.[5][6][7][8]

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".[9]

See also

• Strictosidine
• Bwiti

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. 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.
6. 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.
7. 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.
8. 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.
9. 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.