Voacangine

Voacangine at a Glance

Voacangine is an iboga alkaloid with two claims on attention, and neither is a traditional use.

It is the molecule ibogaine is made from. In the plant it is the biosynthetic precursor; in industry it is the starting material — most semisynthetic ibogaine is produced by decarbomethoxylating voacangine extracted from the seeds and root bark of the West African tree Voacanga africana ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}. Structurally the relationship is a single ester group: voacangine is ibogaine carrying a carbomethoxy group at C-16, and removing it gives ibogaine.

And it blocks the hERG potassium channel more potently than ibogaine does — IC50 about 2.25 µM against 3.53 µM for plant-extracted ibogaine and 4.09 µM for the semisynthetic material ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}. The QT prolongation, torsade de pointes and deaths associated with ibogaine are usually discussed as a problem with ibogaine. They are a property of the iboga scaffold, and the precursor carries it too.

Its own pharmacology is modest and entirely preclinical: an antiangiogenic action through direct binding to VEGFR2, weak acetylcholinesterase inhibition, and antimicrobial activity that arrives together with cytotoxicity.

The Cardiac Liability Belongs to the Scaffold

This is the finding that changes how the iboga family should be discussed.

Whole-cell patch-clamp measurements of hERG (IKr) blockade across the iboga set give a consistent picture ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}:

Compound	hERG IC50	What it is
Voacangine	2.25 ± 0.34 µM	biosynthetic precursor; industrial feedstock
Noribogaine	2.86 ± 0.68 µM	the long-lived human metabolite
Ibogaine (extracted from T. iboga)	3.53 ± 0.16 µM	the plant alkaloid
Ibogaine (semisynthetic, via voacangine)	4.09 ± 0.69 µM	the manufactured drug
18-Methoxycoronaridine (18-MC)	> 50 µM	a designed synthetic congener

Three things follow. First, the precursor is the most potent blocker of the four natural compounds — so the hazard is not a contaminant, a manufacturing artefact or something ibogaine acquired on the way to becoming a drug. Second, purification cannot solve it: extracted and semisynthetic ibogaine differ by less than a factor of two, well inside the range that separates them from each other. Third, chemistry can. 18-MC binds the hERG channel with similar affinity to the others (Ki values across the whole set fall between 0.71 and 3.89 µM) yet produces an IC50 above 50 µM — binding and blocking are separable, and a redesigned molecule can keep the anti-addictive pharmacology without the channel block ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}.

That third point is the one the field has acted on. The oxa-iboga analogues, in which the scaffold itself is rebuilt rather than the plant material purified, disrupt opioid use in animal models without the cardiac risk ^{13Reference 13Havel V et al. · 2024AnimalOxa-iboga alkaloids lack cardiac risk and disrupt opioid use in animal modelsView study →}. The search for a safer iboga drug has meant redesigning the molecule, and the voacangine measurement is a large part of why.

Its Role in the Plant

Voacangine sits at a branch point in monoterpene indole alkaloid biosynthesis that was only worked out recently.

The iboga alkaloids are made exclusively by members of the Apocynaceae, and the enzymes that build the characteristic bicyclic scaffold are carboxylesterase-like [4+2] cyclases: coronaridine synthase in Tabernanthe iboga and catharanthine synthase in Catharanthus roseus, both of which perform regio- and enantiodivergent cycloadditions on a common intermediate that the related enzyme tabersonine synthase turns into the aspidosperma scaffold instead ^{7Reference 7DeMars MD 2nd · 2024Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesisView study →}. Ancestral-sequence reconstruction places tabersonine synthase first, with the iboga-forming enzymes emerging separately in two lineages afterwards — an evolutionary order that matches how these alkaloid types are distributed across the family ^{7Reference 7DeMars MD 2nd · 2024Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesisView study →}.

Voacangine is the methoxylated, carbomethoxy-bearing member of that iboga series, and the ester it carries is not chemically inert. In a direct comparison of the two molecules’ oxidation chemistry, the C-16 carbomethoxy ester stabilises voacangine against oxidation relative to ibogaine, particularly at the indole ring, while simultaneously making the isoquinuclidine nitrogen more reactive ^{8Reference 8González B et al. · 2023Reactivity of the iboga skeleton: oxidation study of ibogaine and voacangineView study →}. The plant’s version of the molecule is therefore the more shelf-stable one, which is convenient for the industry that ships it.

Voacanga africana keeps producing new members of the series: voacandial and voacanginone A, both voacangine-derived and both structurally confirmed by asymmetric total synthesis, were described from its root bark in 2025 ^{9Reference 9Matsumiya S et al. · 2025Voacandial and voacanginone A, iboga-type monoterpenoid indole alkaloids from Voacanga africana root bark: isolation, structure elucidation, and asymmetric total synthesesView study →}.

What It's Used For

Voacangine has never been given to a person as a drug, and its literature is small, in-vitro and mostly incidental — it appears in screens of Voacanga and Tabernaemontana alkaloids where a bis-indole neighbour usually outperforms it. The exception is a genuinely specific target.

A hERG blocker, more potent than ibogaine:IC50 ≈ 2.25 µM, the most potent of the four natural iboga alkaloids measured — which is what makes the cardiac risk a scaffold property rather than an ibogaine problem ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}.

A direct VEGFR2 binder with antiangiogenic activity:inhibits HUVEC proliferation at IC50 ≈ 18 µM without cytotoxicity, suppresses VEGF-induced tube formation and chemoinvasion, lowers HIF-1α and VEGF, and inhibits angiogenesis in the chick chorioallantoic membrane; it binds the VEGFR2 kinase domain directly and has been used as a template for synthetic inhibitors ^{2,3Reference 2Kim Y et al. · 2012In vitroA natural small molecule voacangine inhibits angiogenesis both in vitro and in vivo — in vitro and animal modelView study →Reference 3Cho SM et al. · 2021In vitroDevelopment of novel VEGFR2 inhibitors originating from natural product analogues with antiangiogenic impact — in vitro and miceView study →}.

Weak, unquantified acetylcholinesterase inhibitionin a thin-layer screen of Tabernaemontana australis alkaloids ^{4Reference 4Andrade MT et al. · 2005In vitroIndole alkaloids from Tabernaemontana australis (MuellView study →} — and antimicrobial activity that is real but poor: against Mycobacterium tuberculosis it is fifteen times weaker than the bis-indole voacamine and cytotoxic at the same concentrations ^{5Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →}.

The honest headline:its importance is chemical, not therapeutic. It is the feedstock for semisynthetic ibogaine and the molecule that localised the iboga cardiac hazard to the scaffold — not a candidate medicine in its own right.

Evidence by IndicationStrength of support · Beta

Mechanisms

Target / pathway	Effect	Relevant to
hERG (IKr) potassium channel	blockade, IC50 ≈ 2.25 µM — the most potent of the natural iboga alkaloids	QT prolongation · the scaffold argument
VEGFR2 kinase domain	direct binding; inhibits downstream signalling	antiangiogenic activity
HIF-1α → VEGF	dose-dependent reduction in expression	antiangiogenic activity
Acetylcholinesterase	inhibition, potency uncharacterised	a single qualitative screen
Coronaridine synthase ([4+2] cyclase)	the enzyme that builds the iboga scaffold voacangine belongs to	plant biosynthesis
C-16 carbomethoxy ester	stabilises the indole ring against oxidation; activates the isoquinuclidine nitrogen	chemistry · shelf stability · semisynthesis

The first row is what makes voacangine worth knowing about and the last row is why it is traded. Nothing between them is a therapeutic use.

Pharmacokinetics

There is no pharmacokinetic data for voacangine in humans or animals — no absorption, distribution, metabolism or half-life figures. It has not been administered as a drug, so nothing has been measured.

Two indirect points are worth stating. Its C-16 ester makes it more resistant to oxidation than ibogaine at the indole ring while making the bridgehead nitrogen more reactive ^{8Reference 8González B et al. · 2023Reactivity of the iboga skeleton: oxidation study of ibogaine and voacangineView study →}, which bears on stability rather than on disposition. And by analogy with the rest of the family, hepatic CYP2D6 dominates iboga alkaloid metabolism ^{11Reference 11Litjens RP · 2016ReviewHow toxic is ibogaine? — reviewView study →} — but whether voacangine is a substrate, and what it would be converted to, is unstudied.

Clinical Trials

None, and none proposed. Voacangine has never entered human testing in any indication. Its human relevance is entirely upstream: it is the material from which a drug that has been tested in humans is manufactured ^{1,12Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →Reference 12Mash DC · 2023ReviewIUPHAR invited review — ibogaine: a legacy within the current renaissance of psychedelic therapy — reviewView study →}.

Completed	Planned	Terminated	Preclinical
—	—	—	hERG electrophysiology; VEGFR2 binding and antiangiogenesis; antimycobacterial and antiplasmodial screens; biosynthesis and total synthesis

Last checked: September 2026.

Isolate vs. Plant Studies

Every voacangine result used the purified alkaloid — voacangine isolated from Voacanga africana or Tabernaemontana, tested against cell lines, enzymes and channels ^{1,2,4,5Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →Reference 2Kim Y et al. · 2012In vitroA natural small molecule voacangine inhibits angiogenesis both in vitro and in vivo — in vitro and animal modelView study →Reference 4Andrade MT et al. · 2005In vitroIndole alkaloids from Tabernaemontana australis (MuellView study →Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →}. There are no whole-extract voacangine studies, and there is no traditional preparation of which voacangine is the active.

That matters most for the hERG result, and in a reassuring direction: because the measurement is on the isolate, it cannot be dismissed as a matrix effect, and it applies to the manufacturing feedstock regardless of which plant it came from ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}. Where the isolate framing does bite is on the antimicrobial and antiplasmodial screens, in which the bis-indole alkaloids voacamine and voacorine outperform voacangine substantially ^{5,6Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →Reference 6Babiaka SB et al. · 2025In vitroIboga-indole alkaloids as potential plasmodial inhibitors: identification, biosynthesis, and molecular docking studies — in vitroView study →} — so a Voacanga extract’s activity should not be attributed to voacangine, and a voacangine result should not be read back onto the plant.

Prevalence in Nature

Voacangine is an Apocynaceae alkaloid, restricted to the family that makes iboga-type monoterpene indole alkaloids ^{7Reference 7DeMars MD 2nd · 2024Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesisView study →}.

Its commercially important source is Voacanga africana, a West and Central African tree whose seeds and root bark are the industrial feedstock for semisynthetic ibogaine ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}; the same root bark continues to yield previously undescribed voacangine-derived alkaloids ^{9Reference 9Matsumiya S et al. · 2025Voacandial and voacanginone A, iboga-type monoterpenoid indole alkaloids from Voacanga africana root bark: isolation, structure elucidation, and asymmetric total synthesesView study →}. It occurs in iboga (Tabernanthe iboga) root bark as a minor alkaloid alongside ibogaine, ibogamine, ibogaline and tabernanthine, where it is the biosynthetic precursor of the dominant ibogaine ^{7,12Reference 7DeMars MD 2nd · 2024Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesisView study →Reference 12Mash DC · 2023ReviewIUPHAR invited review — ibogaine: a legacy within the current renaissance of psychedelic therapy — reviewView study →}. It is also reported across the neotropical genus Tabernaemontana — T. australis in Brazil ^{4Reference 4Andrade MT et al. · 2005In vitroIndole alkaloids from Tabernaemontana australis (MuellView study →}, and T. alba and T. arborea in Mexico, where root-bark alkaloid extracts have voacangine and voacamine as their major components ^{5Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →}.

Content figures are not well established for any source. What is documented is that voacangine yield is what makes V. africana seed commercially worth collecting, and that the trade in that seed is the supply chain behind most ibogaine on the market — a point of some importance for iboga conservation, since Tabernanthe iboga itself is under harvesting pressure in Gabon while the West African Voacanga trade supplies the pharmaceutical demand.

Discovery & Synthesis

Voacangine belongs to the classical mid-twentieth-century Apocynaceae alkaloid chemistry, isolated from Voacanga species as one of a set of iboga-type bases; its individual first isolation is not well documented in the accessible literature. What has been settled only recently is everything about how it is made — by plants and by chemists.

The enzymes were identified in 2024. The [4+2] cyclases that build the iboga scaffold — coronaridine synthase in Tabernanthe iboga, catharanthine synthase in Catharanthus roseus — were characterised, along with their evolutionary origin from an ancestral carboxylesterase ^{7Reference 7DeMars MD 2nd · 2024Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesisView study →}.

The asymmetric total syntheses arrived in 2025. Two independent routes were published in the same year: a divergent catalytic asymmetric approach delivering (−)-voacangine and (−)-isovoacangine along with their 3-oxo and 3-cyano relatives, built on an asymmetric Michael/aldol reaction and a ring reorganisation that runs opposite to the proposed biogenetic pathway ^{10Reference 10Lu PP et al. · 2025Synthetic studies on enantioselective total syntheses of tabercarpamines and voacangine-type indole alkaloidsView study →}; and asymmetric total syntheses of the newly isolated voacangine-derived alkaloids voacandial and voacanginone A, which also completed catharanthine ^{9Reference 9Matsumiya S et al. · 2025Voacandial and voacanginone A, iboga-type monoterpenoid indole alkaloids from Voacanga africana root bark: isolation, structure elucidation, and asymmetric total synthesesView study →}.

Manufacture, however, is extraction. Voacangine is not synthesised commercially — it is extracted from Voacanga africana seed and root bark, and its principal commercial fate is conversion to ibogaine by decarbomethoxylation, which is how most of the world’s ibogaine is produced ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}. The molecule’s economic role is as an intermediate, not a product.

Patents: not yet researched.

Toxicity & Safety

Voacangine carries a toxic flag on two independent grounds, neither of which comes from human exposure.

Cardiac. It blocks hERG at IC50 ≈ 2.25 µM, more potently than noribogaine (2.86 µM) or either form of ibogaine (3.53 and 4.09 µM) ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}. hERG blockade is the mechanism behind the QT prolongation, torsade de pointes and fatalities documented for ibogaine ^{11Reference 11Litjens RP · 2016ReviewHow toxic is ibogaine? — reviewView study →}, and there is no reason to expect voacangine to be exempt from a liability it exhibits more strongly. It has never been given to a person, so no QT measurement exists for it — the flag is mechanistic, and appropriately conservative.

Cellular. In the antimycobacterial screen, voacangine’s selectivity index against Vero cells was 1.42 — it was cytotoxic at essentially the concentration at which it was active ^{5Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →}. Ibogaine’s index in the same run was 1.00 and voacamine’s 0.16.

Safety at a Glance

Toxic

The most potent hERG blocker of the natural iboga alkaloids. IC50 ≈ 2.25 µM; the QT liability of this family is a scaffold property, and this molecule carries the strongest version of it.
Cytotoxic at its active concentrations. Selectivity index 1.42 against mammalian cells in the one assay that measured it.
No human data of any kind. No dose, no pharmacokinetics, no safety study, no clinical use. Absence of findings is not evidence of safety.
No reproductive, developmental or repeat-dose toxicology has been published for this molecule.

Full Safety & Interactions Detail

Why the hERG number matters even though nobody takes voacangine. Two reasons. It is present as an impurity or residue in semisynthetic ibogaine preparations made from it, and the semisynthetic material was measured at a slightly higher hERG IC50 than the plant-extracted material ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →} — so the manufacturing route does not remove the class liability. And it is present in Voacanga africana material, which is sold as a botanical in its own right in some markets.

Interactions. None have been studied. On mechanism, the concerns for any hERG-blocking compound apply: additive QT prolongation with other QT-prolonging drugs, and increased risk with hypokalaemia, hypomagnesaemia, bradycardia or congenital long-QT. Because CYP2D6 dominates the metabolism of the iboga alkaloids ^{11Reference 11Litjens RP · 2016ReviewHow toxic is ibogaine? — reviewView study →}, CYP2D6 inhibitors and poor-metaboliser genotypes are plausible risk multipliers for any iboga-family exposure — but this has been demonstrated for ibogaine, not for voacangine.

Reproductive. No data. Not assessed.

Legal. Voacangine is not itself scheduled in most jurisdictions, but it is a direct chemical precursor to ibogaine, which is Schedule I in the United States and controlled elsewhere; precursor legislation may apply. Check locally.

Dosage

There is no dose. Voacangine has never been administered to humans as a medicine, so no therapeutic, research or traditional dose exists.

The only quantities on record are laboratory concentrations:

Measurement	Value
hERG (IKr) blockade, IC50	≈ 2.25 µM ^{1Reference 1Alper K et al. · 2016In vitrohERG blockade by iboga alkaloids — in vitroView study →}
HUVEC antiproliferation, IC50	≈ 18 µM ^{2Reference 2Kim Y et al. · 2012In vitroA natural small molecule voacangine inhibits angiogenesis both in vitro and in vivo — in vitro and animal modelView study →}
M. tuberculosis H37Rv, MIC100	250 µg/mL ^{5Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →}
Vero-cell selectivity index	1.42 ^{5Reference 5Guzmán-Gutiérrez SL et al. · 2022In vitroAntimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitroView study →}

These are in-vitro figures and are not a personal recommendation. Voacangine’s practical existence is as chemical feedstock, and it should be treated as a reagent rather than as a supplement.

References

Alper K, Bai R, Liu N, et al. (2016). hERG blockade by iboga alkaloids — in vitro. Cardiovascular Toxicology. https://pubmed.ncbi.nlm.nih.gov/25636206/
Kim Y, Jung HJ, Kwon HJ (2012). A natural small molecule voacangine inhibits angiogenesis both in vitro and in vivo — in vitro and animal model. Biochemical and Biophysical Research Communications. https://pubmed.ncbi.nlm.nih.gov/22155252/
Cho SM, Kim Y, Jung Y, et al. (2021). Development of novel VEGFR2 inhibitors originating from natural product analogues with antiangiogenic impact — in vitro and mice. Journal of Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/34730352/
Andrade MT, Lima JA, Pinto AC, et al. (2005). Indole alkaloids from Tabernaemontana australis (Muell. Arg) Miers that inhibit acetylcholinesterase enzyme — in vitro. Bioorganic & Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/15911323/
Guzmán-Gutiérrez SL, Silva-Miranda M, Krengel F, et al. (2022). Antimycobacterial activity of alkaloids and extracts from Tabernaemontana alba and T. arborea — in vitro. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/32392600/
Babiaka SB, Lahngong MS, Simoben CV, et al. (2025). Iboga-indole alkaloids as potential plasmodial inhibitors: identification, biosynthesis, and molecular docking studies — in vitro. Chemistry & Biodiversity. https://pubmed.ncbi.nlm.nih.gov/41135012/
DeMars MD 2nd, O’Connor SE (2024). Evolution and diversification of carboxylesterase-like [4+2] cyclases in aspidosperma and iboga alkaloid biosynthesis. Proceedings of the National Academy of Sciences. https://pubmed.ncbi.nlm.nih.gov/38319969/
González B, Veiga N, Hernández G, et al. (2023). Reactivity of the iboga skeleton: oxidation study of ibogaine and voacangine. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/37221656/
Matsumiya S, Iwai M, Asaba KN, et al. (2025). Voacandial and voacanginone A, iboga-type monoterpenoid indole alkaloids from Voacanga africana root bark: isolation, structure elucidation, and asymmetric total syntheses. Journal of Organic Chemistry. https://pubmed.ncbi.nlm.nih.gov/40876041/
Lu PP, Tan DX, Han FS (2025). Synthetic studies on enantioselective total syntheses of tabercarpamines and voacangine-type indole alkaloids. Chemistry — A European Journal. https://pubmed.ncbi.nlm.nih.gov/40281646/
Litjens RP, Brunt TM (2016). How toxic is ibogaine? — review. Clinical Toxicology. https://pubmed.ncbi.nlm.nih.gov/26807959/
Mash DC (2023). IUPHAR invited review — ibogaine: a legacy within the current renaissance of psychedelic therapy — review. Pharmacological Research. https://pubmed.ncbi.nlm.nih.gov/36907284/
Havel V, Kruegel AC, Bechand B, et al. (2024). Oxa-iboga alkaloids lack cardiac risk and disrupt opioid use in animal models. Nature Communications. https://doi.org/10.1038/s41467-024-51856-y