iboga-type alkaloid

{{Short description|Group of alkaloids related to Tabernanthe iboga}}

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.{{Cite journal |last1=Glick |first1=S. D. |last2=Kuehne |first2=M. E. |last3=Raucci |first3=J. |last4=Wilson |first4=T. E. |last5=Larson |first5=D. |last6=Keller |first6=R. W. |last7=Carlson |first7=J. N. |date=1994-09-19 |title=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 |url=https://dx.doi.org/10.1016/0006-8993%2894%2990948-2 |journal=Brain Research |language=en |volume=657 |issue=1 |pages=14–22 |doi=10.1016/0006-8993(94)90948-2 |pmid=7820611 |s2cid=1940631 |issn=0006-8993 |access-date=2023-08-06 |archive-date=2023-08-06 |archive-url=https://web.archive.org/web/20230806133833/https://www.sciencedirect.com/science/article/abs/pii/0006899394909482?via%3Dihub |url-status=live |url-access=subscription }}{{Cite journal |last1=Antonio |first1=Tamara |last2=Childers |first2=Steven R. |last3=Rothman |first3=Richard B. |last4=Dersch |first4=Christina M. |last5=King |first5=Christine |last6=Kuehne |first6=Martin |last7=Bornmann |first7=William G. |last8=Eshleman |first8=Amy J. |last9=Janowsky |first9=Aaron |last10=Simon |first10=Eric R. |last11=Reith |first11=Maarten E. A. |last12=Alper |first12=Kenneth |date=2013-10-16 |title=Effect of Iboga Alkaloids on µ-Opioid Receptor-Coupled G Protein Activation |journal=PLOS ONE |language=en |volume=8 |issue=10 |pages=e77262 |doi=10.1371/journal.pone.0077262 |issn=1932-6203 |pmc=3818563 |pmid=24204784 |bibcode=2013PLoSO...877262A |doi-access=free }}

Naturally-occurring

(16R,20S)-Ibogaine Structural Formula V2.svg|Ibogaine

(16R,20S)-Ibogamine Structural Formula V2.svg|Ibogamine

(16R,20S)-Tabernanthine Structural Formula V2.svg|Tabernanthine

(16S,20S)-Coronaridine Structural Formula V2.svg|Coronaridine

=Substituted ibogamines=

File:Naturally_occurring_substituted_ibogamines.png

class="wikitable"

! PubChem {{abbr|CID|Compound ID}}

! Name

! R1

! R2

! R3

! R4

[https://pubchem.ncbi.nlm.nih.gov/compound/100217 100217]

| Ibogamine

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/197060 197060]

| Ibogaine

| OMe

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/3083548 3083548]

| Noribogaine

| OH

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/6326116 6326116]

| Tabernanthine

| H

| OMe

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/193302 193302]

| Ibogaline

| OMe

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/73489 73489]

| Coronaridine

| H

| CO₂Me

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/73255 73255]

| Voacangine

| OMe

| H

| CO₂Me

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/363281 363281]

| Isovoacangine

| H

| OMe

| CO₂Me

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/65572 65572]

| Conopharyngine

| OMe

| CO₂Me

| H

[https://pubchem.ncbi.nlm.nih.gov/compound/11077316 11077316]

| 19(S)-Hydroxyibogamine

| H

| OH

[https://pubchem.ncbi.nlm.nih.gov/compound/71656190 71656190]

| Iboxygaine / Kimvuline

| OMe

| H

| OH

| {{abbr|ND|No data}}

| H

| OMe

| H

| OH

| {{abbr|ND|No data}}

| OMe

| H

| OH

[https://pubchem.ncbi.nlm.nih.gov/compound/15559732 15559732]

| 19(S)-Hydroxycoronaridine

| H

| CO₂Me

| OH

[https://pubchem.ncbi.nlm.nih.gov/compound/196982 196982]

| Voacristine

| OMe

| H

| CO₂Me

| OH

[https://pubchem.ncbi.nlm.nih.gov/compound/10362598 10362598]

| Isovoacristine

| H

| OMe

| CO₂Me

| OH

[https://pubchem.ncbi.nlm.nih.gov/compound/102004638 102004638]

| 19(S)-Hydroxyconopharyngine

| OMe

| CO₂Me

| OH

Catharanthine is an unsaturated analog of coronaridine.

=Oxidation products=

Similarly to other ring-constrained tryptamines such as yohimbine{{Cite journal |last1=Finch |first1=Neville |last2=Gemenden |first2=C. W. |last3=Hsu |first3=Iva Hsiu-Chu |last4=Kerr |first4=Ann |last5=Sim |first5=G. A. |last6=Taylor |first6=W. I. |date=May 1965 |title=Oxidative Transformations of Indole Alkaloids. III. Pseudoindoxyls from Yohimbinoid Alkaloids and Their Conversion to "Invert" Alkaloids 1,2 |url=https://pubs.acs.org/doi/abs/10.1021/ja01088a024 |journal=Journal of the American Chemical Society |language=en |volume=87 |issue=10 |pages=2229–2235 |doi=10.1021/ja01088a024 |pmid=14290283 |bibcode=1965JAChS..87.2229F |issn=0002-7863 |access-date=2023-08-05 |archive-date=2023-02-07 |archive-url=https://web.archive.org/web/20230207112446/https://pubs.acs.org/doi/abs/10.1021/ja01088a024 |url-status=live |url-access=subscription }} and mitragynine (see mitragynine pseudoindoxyl), oxidation and rearrangement products of substituted ibogamines have been reported, such as iboluteine (ibogaine pseudoindoxyl) ([https://pubchem.ncbi.nlm.nih.gov/compound/21589055 CID:21589055]) and voaluteine ([https://pubchem.ncbi.nlm.nih.gov/compound/633439 CID:633439]).{{Cite book |url=https://books.google.com/books?id=AacNdaWmf-8C&dq=ibogaine+pseudoindoxyl&pg=PA81 |title=The Alkaloids: Chemistry and Physiology V11 |date=2014-05-14 |publisher=Academic Press |isbn=978-0-08-086535-5 |language=en |access-date=2023-08-06 |archive-date=2023-08-06 |archive-url=https://web.archive.org/web/20230806133758/https://books.google.com/books?id=AacNdaWmf-8C&dq=ibogaine+pseudoindoxyl&pg=PA81 |url-status=live }}File:Iboga-type pseudoindoxyls.png

=Other alkaloids=

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.{{citation|access-date=2022-07-05 |author=Patrick Köck, Katharina Froelich, Marc Walter, Undine Lang, Kenneth M. Dürsteler |date=July 2022 |doi=10.1016/j.jsat.2021.108717 |pages=108717 |periodical=Journal of Substance Abuse Treatment |title=A systematic literature review of clinical trials and therapeutic applications of ibogaine |url=https://linkinghub.elsevier.com/retrieve/pii/S0740547221004438 |volume=138|pmid=35012793 }}

Synthetic analogues

18-MC, ME-18-MC, and 18-MAC are coronaridine analogs with similar anti-addictive effects.{{cite journal |display-authors=6 |vauthors=Kuehne ME, He L, Jokiel PA, Pace CJ, Fleck MW, Maisonneuve IM, Glick SD, Bidlack JM |date=June 2003 |title=Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents |journal=Journal of Medicinal Chemistry |volume=46 |issue=13 |pages=2716–30 |doi=10.1021/jm020562o |pmid=12801235}}{{cite journal |vauthors=Pace CJ, Glick SD, Maisonneuve IM, He LW, Jokiel PA, Kuehne ME, Fleck MW |date=May 2004 |title=Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration |journal=European Journal of Pharmacology |volume=492 |issue=2–3 |pages=159–67 |doi=10.1016/j.ejphar.2004.03.062 |pmid=15178360}}{{cite journal |vauthors=Glick SD, Kuehne ME, Maisonneuve IM, Bandarage UK, Molinari HH |date=May 1996 |title=18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats |journal=Brain Research |volume=719 |issue=1–2 |pages=29–35 |doi=10.1016/0006-8993(96)00056-X |pmid=8782860 |s2cid=6178161}}{{cite journal |vauthors=Glick SD, Sell EM, Maisonneuve IM |date=December 2008 |title=Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration |journal=European Journal of Pharmacology |volume=599 |issue=1–3 |pages=91–5 |doi=10.1016/j.ejphar.2008.09.038 |pmc=2600595 |pmid=18930043}}

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".{{Cite journal |last1=Cameron |first1=Lindsay P. |last2=Tombari |first2=Robert J. |last3=Lu |first3=Ju |last4=Pell |first4=Alexander J. |last5=Hurley |first5=Zefan Q. |last6=Ehinger |first6=Yann |last7=Vargas |first7=Maxemiliano V. |last8=McCarroll |first8=Matthew N. |last9=Taylor |first9=Jack C. |last10=Myers-Turnbull |first10=Douglas |last11=Liu |first11=Taohui |last12=Yaghoobi |first12=Bianca |last13=Laskowski |first13=Lauren J. |last14=Anderson |first14=Emilie I. |last15=Zhang |first15=Guoliang |date=January 2021 |title=A non-hallucinogenic psychedelic analogue with therapeutic potential |journal=Nature |language=en |volume=589 |issue=7842 |pages=474–479 |doi=10.1038/s41586-020-3008-z |issn=1476-4687 |pmc=7874389 |pmid=33299186|bibcode=2021Natur.589..474C }}