Apparicine

Apparicine at a Glance

Apparicine — also, and equally correctly, pericalline — is a monoterpenoid indole alkaloid (MIA) of the dogbane family, Apocynaceae. It was first characterised in 1965 from an Aspidosperma species and named for the Brazilian botanist Apparicio Duarte ^{1Reference 1Joule JA et al. · 1965Alkaloid studiesView study →}. Its verified home genera are Aspidosperma, Tabernaemontana (including the species still often published under Ervatamia), and a handful of relatives: Vallesia, Ochrosia, Kopsia and Trachelospermum ^{8,10,12,13,15,16,17,19Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →Reference 10Höft M et al. · 1998Leaf alkaloid contents of Tabernaemontana pachysiphon as influenced by endogenous and environmental factors in the natural habitatView study →Reference 12Crooks PA · 1970The isolation and identification of (−)-apparicine from Tabernaemontana cumminsiiView study →Reference 13Atta-ur-Rahman et al. · 1984Isolation of apparicine from the leaves of Ervatamia coronariaView study →Reference 15Zèches M et al. · 1995Alkaloids from leaves and stems of Vallesia glabraView study →Reference 16Fatima T et al. · 1987Indole alkaloids from Trachelospermum jasminoidesView study →Reference 17Carroll AR et al. · 2008Alkaloids from the Australian rainforest tree Ochrosia mooreiView study →Reference 19Kalshetti MG · 2020ReviewThe indole-based subincanadine alkaloids and their biogenetic congenersView study →}.

Structurally it is the interesting one. Apparicine was the first “5-nor stemmadenine” alkaloid ever isolated and solved — a small group of MIAs in which one of the two carbons that tryptamine normally contributes to the skeleton has been excised, leaving a single-carbon bridge and a strained 1-azabicyclo[4.2.2]decane cage ^{3,4Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →Reference 4Bennasar ML et al. · 2009Total synthesis of the bridged indole alkaloid apparicineView study →}. That missing carbon is the most genuinely notable thing about the molecule, and it took chemists until 2009 to build it in the laboratory ^{5Reference 5Bennasar ML et al. · 2009The first total synthesis of (±)-apparicineView study →}.

Pharmacologically it is thin, and honestly so. Three isolate findings exist, each from a single laboratory: micromolar opioid-receptor affinity with analgesia in mice ^{6Reference 6Ingkaninan K et al. · 1999Isolation of opioid-active compounds from Tabernaemontana pachysiphon leavesView study →}, potent inhibition of xanthine oxidase in a test tube ^{7Reference 7Shi BB et al. · 2019Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activityView study →}, and modest antiplasmodial activity offset by its own cytotoxicity ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}. There is no pharmacokinetic data of any kind, no toxicology, and no human study. It is a phytochemistry-and-total-synthesis molecule, not a therapeutic one.

Apparicine Is Not a Vinca Alkaloid

This page exists because apparicine appeared in a Vinca minor research note, so the attribution has to be settled explicitly.

It has not been isolated from Vinca. A PubMed search for apparicine AND Vinca returns exactly one record (checked July 2026): Mai and colleagues’ 2025 study of two promiscuous V. minor cytochrome P450 hydroxylases ^{9Reference 9Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →}. In that work, apparicine is a substrate fed to an enzyme in vitro, not a metabolite detected in the plant. The whole point of the paper is that VmV10H is promiscuous — it hydroxylates “structurally diverse MIAs” at C-10 — and apparicine is one of the diverse structures used to demonstrate that breadth, alongside vincaminoreine, pericyclivine and akuammidine ^{9Reference 9Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →}. Enzyme promiscuity is evidence about the enzyme’s active site. It is not evidence that the substrate occurs in the plant the enzyme came from.

Consistent with that, apparicine is not listed among lesser periwinkle’s constituents, and it should stay that way unless a phytochemical isolation from Vinca is published. The extraction note that flagged it said as much at the time.

Two further separations are worth stating plainly, because periwinkle nomenclature is a minefield:

• This is not vincristine or vinblastine. Those are bisindole alkaloids from Catharanthus roseus (Madagascar periwinkle) — a different genus, a different structural class, and licensed cytotoxic chemotherapy. Apparicine is a monomeric MIA with no chemotherapeutic role. A cell-viability screen here is a screening assay, not a cancer claim.
• This is not vincamine or vinpocetine. Those belong to the eburnamine–vincamine series that genuinely defines Vinca minor. Apparicine shares neither their skeleton nor their pharmacology.

There is one legitimate Catharanthus connection, and it is a footnote rather than a headline: pericalline — proven identical to apparicine in 1969 ^{2Reference 2Farnsworth NR · 1969Identity of pericalline, tabernoschizine, apparicine and gomezineView study →} — was isolated from the roots of Catharanthus trichophyllus, a minor species, in 1974 ^{20Reference 20Segelman AB · 1974Catharanthus alkaloids XXXI: isolation of ajmalicine, pericalline, tetrahydroalstonine, vindolinine, and ursolic acid from Catharanthus trichophyllus rootsView study →}. That is a different plant from C. roseus and a different plant again from Vinca minor.

The Missing Carbon: A 5-Nor Skeleton

Almost every monoterpenoid indole alkaloid is assembled from tryptamine plus a monoterpene unit (secologanin). Tryptamine donates the indole ring and a two-carbon bridge — biogenetic positions C-5 and C-6 — that links the indole to the aliphatic nitrogen. Apparicine breaks that rule: C-5 is gone, leaving only a single carbon connecting the indole to the nitrogen ^{3Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →}.

The consequences are structural and immediate:

• The molecular formula is C₁₈H₂₀N₂ (MW 264.4) — one carbon short of the usual MIA count.
• The one-carbon bridge forces a strained 1-azabicyclo[4.2.2]decane cage, described in the total-synthesis literature as the defining architectural feature of the class ^{3,4Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →Reference 4Bennasar ML et al. · 2009Total synthesis of the bridged indole alkaloid apparicineView study →}.
• An exocyclic methylene sits at C-16 and an ethylidene at C-20, both of which the synthetic routes have to install late and stereospecifically ^{4Reference 4Bennasar ML et al. · 2009Total synthesis of the bridged indole alkaloid apparicineView study →}.

Apparicine was the first member of this group to be isolated and structurally established ^{1,3Reference 1Joule JA et al. · 1965Alkaloid studiesView study →Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →}, and the group is now named after it — the apparicine class, or 5-nor stemmadenine alkaloids, of which roughly 22 members are known, essentially all from Tabernaemontana ^{3Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →}. The wider family Alvarez and Joule review alongside it (ellipticine, uleine) shares the same theme of carbon loss from the tryptamine bridge ^{22Reference 22Alvarez M · 2001ReviewEllipticine, uleine, apparicine, and related alkaloidsView study →}.

How the Carbon Is Thought to Be Lost

The biosynthesis is inferred, not demonstrated. No enzyme, gene or labelled-precursor study for apparicine formation has been published. What exists is a well-supported biomimetic argument:

• The accepted precursor is stemmadenine, the branch-point intermediate of MIA metabolism — hence the class name 5-nor stemmadenine. The C-5 tryptamine atom is proposed to be excised oxidatively ^{3Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →}.
• Pericine (also called apparicine’s dihydro relative in some series) sits immediately upstream: Lim, Low and Kam showed in 2006 that a biomimetic oxidative transformation of pericine partially synthesises apparicine, and in the same work generates valparicine, a new pentacyclic alkaloid from Kopsia ^{21Reference 21Lim KH et al. · 2006Biomimetic oxidative transformations of pericine: partial synthesis of apparicine and valparicine, a new pentacyclic indole alkaloid from KopsiaView study →}. This is the strongest experimental support the pathway has.
• A parallel proposal routes several Kopsia arborea alkaloids — apparicine, valparicine, arboridinine, arborisidine and arbornamine — from subincanadine E as a common biogenetic precursor ^{19Reference 19Kalshetti MG · 2020ReviewThe indole-based subincanadine alkaloids and their biogenetic congenersView study →}.

Gap: every step above is chemical inference or in-plant co-occurrence logic. Nobody has identified the oxidase that removes C-5, and no isotope-labelling experiment has tracked the carbon out. That is the single largest open question about this molecule.

What It's Used For

Three findings on the isolated molecule are scoreable, each resting on a single paper from a single group. There is no replication, no dose–response work in animals beyond one screen, and no human data at all.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here is capped low by the same fact: one laboratory, one paper, no replication, no human data.

01Opioid-Receptor Binding & In-Vivo AnalgesiaShaky30%Isolate: K_i 2.65 µM at the opiate receptor + mouse writhing test, single 1999 report ^{6Reference 6Ingkaninan K et al. · 1999Isolation of opioid-active compounds from Tabernaemontana pachysiphon leavesView study →}

02Xanthine-Oxidase InhibitionShaky22%Isolate, in vitro only: IC₅₀ 0.65 µM vs allopurinol 0.60 µM, single 2019 report ^{7Reference 7Shi BB et al. · 2019Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activityView study →}

03Antiplasmodial ActivityShaky18%Isolate, in vitro: IC₅₀ ~3.0 µg/mL against chloroquine-resistant P. falciparum, SI 14 ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}

Mechanisms

The two rows at the bottom are the ones most likely to be mis-cited later. A docking score is a prediction, and a promiscuous enzyme accepting a substrate is a statement about the enzyme.

Pharmacokinetics

There is none. A PubMed search for apparicine AND (pharmacokinetics OR bioavailability) returns zero records (checked July 2026). No absorption study, no oral bioavailability figure, no distribution, no metabolism, no half-life, no identified metabolite, no plasma concentration in any species. The one metabolic transformation ever measured on the molecule is a heterologous C-10 hydroxylation by a plant cytochrome P450, performed in vitro to characterise the enzyme ^{9Reference 9Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →} — plant biochemistry, not mammalian pharmacokinetics.

This absence is load-bearing for everything above. Micromolar receptor affinity and a sub-micromolar enzyme IC₅₀ mean nothing without knowing whether the molecule is absorbed at all, and there is currently no way to find out from the literature.

Clinical Trials

None, at any stage. Apparicine has never entered a human study, and no trial registration or investigational programme could be located. Every result here is preclinical, and most of it is cell-free.

Last checked: July 2026.

Isolate vs. Plant Studies

Unusually for a page this thin, the evidence is almost entirely on the isolate — which is a strength of the data quality even though the quantity is small. In all three scoreable findings the compound was purified to a single substance before it was tested: from T. pachysiphon leaves for the opioid work ^{6Reference 6Ingkaninan K et al. · 1999Isolation of opioid-active compounds from Tabernaemontana pachysiphon leavesView study →}, from T. bufalina aerial parts for the xanthine-oxidase screen ^{7Reference 7Shi BB et al. · 2019Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activityView study →}, and from A. olivaceum bark and leaves for the antiplasmodial assay ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}. Nothing here is an “extract contains apparicine, extract does X” inference.

The one place that discipline breaks down is the cytotoxicity literature, and it should be read sceptically. Hullatti and colleagues found that the alkaloid fraction of Ervatamia coronaria (= Tabernaemontana divaricata) was cytotoxic to HT-29, A-549 and MCF-7 cells, and speculated that “alkaloids such as ervatamine, apparicine and coronaridine that were earlier reported may be responsible” ^{24Reference 24Hullatti K et al. · 2013Bioactivity-guided isolation of cytotoxic constituents from three medicinal plantsView study →}. That is a fraction-level result with an unattributed guess appended — apparicine was neither isolated nor tested in that work. Similarly, the bisindole alkaloid flabellipparicine from T. divaricata contains an apparicine-derived half, but the cytotoxic compounds in that paper were other alkaloids entirely, and apparicine itself was among the known compounds without a reported hit ^{18Reference 18Cai YS et al. · 2018Flabellipparicine, a flabelliformide-apparicine-type bisindole alkaloid from Tabernaemontana divaricataView study →}.

The reverse transfer is worth noting too: apparicine’s own measured cytotoxicity (HepG2 MDL₅₀ 41 µg/mL) ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →} is what stops its antiplasmodial number from being interesting. In this molecule’s case, isolate testing has mostly served to deflate claims that whole-fraction work would have inflated.

Prevalence in Nature

Apparicine is an Apocynaceae molecule and, so far as the indexed literature shows, only an Apocynaceae molecule. The confirmed occurrences, by genus:

Aspidosperma — the discovery genus. The 1965 structure paper describes it as “a novel Aspidosperma alkaloid” ^{1Reference 1Joule JA et al. · 1965Alkaloid studiesView study →}, and it is one of the four principal MIAs of A. olivaceum bark and leaves, a Brazilian antipyretic bark ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}.

Tabernaemontana — by far the largest share of reports, and the genus the whole 5-nor stemmadenine class is associated with ^{3Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →}:

• T. pachysiphon — apparicine is one of the quantitatively predominant leaf alkaloids, alongside tubotaiwine, tubotaiwine-N-oxide and isovoacangine. Höft and colleagues tracked it across a Kenyan population and in glasshouse trials, finding content varied with site, leaf age, crown position and plant age, was highest in young leaves, rose with nutrient supply and with drought, and fell under high light ^{10,11Reference 10Höft M et al. · 1998Leaf alkaloid contents of Tabernaemontana pachysiphon as influenced by endogenous and environmental factors in the natural habitatView study →Reference 11Höft M et al. · 1996Growth and alkaloid contents in leaves of Tabernaemontana pachysiphon Stapf (Apocynaceae) as influenced by light intensity, water and nutrient supplyView study →}.
• T. cumminsii — the source of the first explicit (−)-apparicine isolation and identification ^{12Reference 12Crooks PA · 1970The isolation and identification of (−)-apparicine from Tabernaemontana cumminsiiView study →}.
• T. divaricata (published historically as Ervatamia coronaria) — isolated from the leaves ^{13Reference 13Atta-ur-Rahman et al. · 1984Isolation of apparicine from the leaves of Ervatamia coronariaView study →}; also the source of the apparicine-derived bisindole flabellipparicine ^{18Reference 18Cai YS et al. · 2018Flabellipparicine, a flabelliformide-apparicine-type bisindole alkaloid from Tabernaemontana divaricataView study →}.
• T. bufalina — among 74 known alkaloids recovered from the aerial parts ^{7Reference 7Shi BB et al. · 2019Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activityView study →}.
• Ervatamia yunnanensis — recovered in the largest single quantity of any MIA in a preparative separation: 112 mg of >95%-pure apparicine from 2.1 g of crude extract, versus 15 mg of isovoacangine ^{14Reference 14Zhou J et al. · 2019Preparative separation of monoterpenoid indole alkaloid epimers from Ervatamia yunnanensis Tsiang by pH-zone-refining counter-current chromatography combined with preparative high-performance liquid chromatographyView study →}. This is a purification yield, not a plant concentration, but it indicates a genuinely abundant constituent.

Other genera:

• Vallesia glabra (Bolivia) — one of eleven known indole alkaloids from leaves and stems ^{15Reference 15Zèches M et al. · 1995Alkaloids from leaves and stems of Vallesia glabraView study →}.
• Trachelospermum jasminoides (star jasmine) — leaves and stems, with published ¹³C-NMR data ^{16Reference 16Fatima T et al. · 1987Indole alkaloids from Trachelospermum jasminoidesView study →}.
• Ochrosia moorei (Australian rainforest) — from the leaf extract ^{17Reference 17Carroll AR et al. · 2008Alkaloids from the Australian rainforest tree Ochrosia mooreiView study →}.
• Kopsia arborea (Malaysia) — reported alongside valparicine, arboridinine, arborisidine and arbornamine ^{19Reference 19Kalshetti MG · 2020ReviewThe indole-based subincanadine alkaloids and their biogenetic congenersView study →}.
• Catharanthus trichophyllus — reported as pericalline from the roots ^{20Reference 20Segelman AB · 1974Catharanthus alkaloids XXXI: isolation of ajmalicine, pericalline, tetrahydroalstonine, vindolinine, and ursolic acid from Catharanthus trichophyllus rootsView study →}, with the pericalline/apparicine identity established separately ^{2Reference 2Farnsworth NR · 1969Identity of pericalline, tabernoschizine, apparicine and gomezineView study →}.

Not reported from Vinca. See the attribution section above.

No concentration figure exists. Despite Höft’s two quantitative studies of T. pachysiphon ^{10,11Reference 10Höft M et al. · 1998Leaf alkaloid contents of Tabernaemontana pachysiphon as influenced by endogenous and environmental factors in the natural habitatView study →Reference 11Höft M et al. · 1996Growth and alkaloid contents in leaves of Tabernaemontana pachysiphon Stapf (Apocynaceae) as influenced by light intensity, water and nutrient supplyView study →}, no published source states apparicine content as a % dry weight or mg/g in a form that could be cited here.

Discovery & Synthesis

First isolation and structure (1965). Apparicine’s structure was solved by Joule, Monteiro, Durham, Gilbert and Djerassi and published in the Journal of the Chemical Society as the 48th paper in their alkaloid-studies series, under the title “the structure of apparicine, a novel Aspidosperma alkaloid” ^{1Reference 1Joule JA et al. · 1965Alkaloid studiesView study →}. The name honours Apparicio Duarte, the Brazilian botanist associated with the Aspidosperma material. It was the first 5-nor stemmadenine alkaloid to be isolated and characterised ^{3Reference 3Noguchi Y et al. · 2016Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloidView study →}.

The synonym pile-up (1969). Because several groups were working the same Apocynaceae genera in parallel, the molecule was independently named four times. Farnsworth and Fong settled it in 1969, showing that pericalline, tabernoschizine, apparicine and gomezine are one compound ^{2Reference 2Farnsworth NR · 1969Identity of pericalline, tabernoschizine, apparicine and gomezineView study →}. Pericalline remains common in the Catharanthus literature ^{20Reference 20Segelman AB · 1974Catharanthus alkaloids XXXI: isolation of ajmalicine, pericalline, tetrahydroalstonine, vindolinine, and ursolic acid from Catharanthus trichophyllus rootsView study →}; apparicine is the name that stuck everywhere else.

Total synthesis (2009). The strained cage resisted synthesis for 44 years. Bennasar and co-workers at the University of Barcelona reported the first total synthesis of (±)-apparicine in 2009, first in Chemical Communications ^{5Reference 5Bennasar ML et al. · 2009The first total synthesis of (±)-apparicineView study →} and then in full in the Journal of Organic Chemistry ^{4Reference 4Bennasar ML et al. · 2009Total synthesis of the bridged indole alkaloid apparicineView study →}. The route assembles the tricyclic ABC substructure by either an indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclisation, then closes the 1-azabicyclo[4.2.2]decane framework with an intramolecular vinyl-halide Heck reaction that installs both exocyclic alkylidene groups in the same step ^{4Reference 4Bennasar ML et al. · 2009Total synthesis of the bridged indole alkaloid apparicineView study →}. Chauhan and Weinreb later published a much shorter convergent entry to the tetracyclic core of the apparicine class — four steps, 80% overall yield, via an intermolecular nitrosoalkene conjugate addition — though to the core rather than the natural product ^{25Reference 25Chauhan PS · 2014Convergent approach to the tetracyclic core of the apparicine class of indole alkaloids via a key intermolecular nitrosoalkene conjugate additionView study →}. A partial (biomimetic) synthesis from pericine predates both ^{21Reference 21Lim KH et al. · 2006Biomimetic oxidative transformations of pericine: partial synthesis of apparicine and valparicine, a new pentacyclic indole alkaloid from KopsiaView study →}.

Manufacture today: none. Apparicine is not produced commercially in any form. It exists as a research isolate obtained by chromatographic separation from Apocynaceae plant material ^{14Reference 14Zhou J et al. · 2019Preparative separation of monoterpenoid indole alkaloid epimers from Ervatamia yunnanensis Tsiang by pH-zone-refining counter-current chromatography combined with preparative high-performance liquid chromatographyView study →}, and as a synthetic target of academic interest.

Patents: not yet researched.

Toxicity & Safety

Apparicine carries a moderate flag, and the reasoning should be read carefully because it is inferential rather than toxicological. There is no toxicology of any kind on this molecule — no acute, repeat-dose, genotoxicity, reproductive/developmental or interaction study exists. The badge rests on two things that are documented: a measured cytotoxicity to human liver cells (HepG2 MDL₅₀ 41 µg/mL) that the measuring authors described as “moderately toxic” and that was severe enough to sink the compound’s therapeutic window against malaria parasites ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}, and demonstrated CNS activity — opioid-receptor binding with a behavioural analgesic effect in mice ^{6Reference 6Ingkaninan K et al. · 1999Isolation of opioid-active compounds from Tabernaemontana pachysiphon leavesView study →}. A molecule that is cytotoxic to hepatocytes and active at opioid receptors is not one to treat as inert.

Safety at a Glance

⚠️ Moderate toxicity

• Cytotoxic to human liver cells at achievable assay concentrations. HepG2 MDL₅₀ 41 µg/mL; the study authors classed it as moderately toxic and its low selectivity index (14) is a direct consequence ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}.
• Active at opioid receptors, with a behavioural effect in animals. Micromolar binding plus analgesia in the mouse writhing test ^{6Reference 6Ingkaninan K et al. · 1999Isolation of opioid-active compounds from Tabernaemontana pachysiphon leavesView study →} — the receptor subtype, the direction of the effect and any dependence or respiratory liability are all uncharacterised.
• No toxicology exists. No acute, repeat-dose, genotoxicity, reproductive or interaction study has been performed. The moderate grading means plausibly hazardous and untested, not characterised as moderately hazardous.
• No pharmacokinetics, so no exposure argument is possible. Absorption, metabolism and half-life are entirely unknown, in every species ^{9Reference 9Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →}.

Full Safety & Interactions Detail

Measured cytotoxicity. The only quantitative toxicity datum for apparicine is from the Aspidosperma olivaceum antimalarial study: MDL₅₀ 41 ± 2.8 µg/mL against the HepG2 human hepatoma line, by MTT assay ^{8Reference 8Chierrito TP et al. · 2014Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceumView study →}. In the same paper, only two of six plant fractions were toxic to HepG2, and apparicine sat among the compounds the authors identified as limiting because of “their higher toxicities”. This is a cell-viability screen, not a hepatotoxicity assessment — but it is the only number that exists, and it points the wrong way.

Neuroactivity. Apparicine crosses into pharmacologically meaningful territory at the opioid receptor (K_i 2.65 µM) and at adenosine receptors, and produced analgesia in mice ^{6Reference 6Ingkaninan K et al. · 1999Isolation of opioid-active compounds from Tabernaemontana pachysiphon leavesView study →}. No study has examined tolerance, dependence, respiratory depression, sedation, or interaction with opioid analgesics. Any co-exposure with opioid or adenosinergic drugs is entirely uncharacterised — the concern is theoretical, but so is the reassurance.

Enzyme interactions. No CYP450 inhibition or induction screen has been run on apparicine in any mammalian system, and no transporter (P-gp, BCRP) work exists. The only enzyme interaction on record is inhibition of xanthine oxidase (IC₅₀ 0.65 µM) ^{7Reference 7Shi BB et al. · 2019Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activityView study →}, which is a target rather than a liability — but xanthine oxidase also metabolises azathioprine and 6-mercaptopurine, so a potent inhibitor is not a pharmacologically neutral thing. No such interaction has been tested.

Reproductive note (prose only). No reproductive or developmental toxicity study of any kind exists for apparicine. Pregnancy and lactation decisions belong to the herb or product page where intake is actually decided, not to a molecule-level phytochemistry page. Nothing here should be read as an assessment either way.

What is not known. Silence in this section reflects the absence of studies, not the absence of risk. Every safety statement above is either a single measured number or an explicit acknowledgement that nothing has been measured.

Dosage

No dose has been established, studied or proposed for apparicine in humans. There is no supplement, no standardised extract, no clinical protocol, and no traditional preparation attributed to this molecule specifically — the plants that contain it (Aspidosperma barks, Tabernaemontana leaves) are used traditionally as whole preparations whose effects belong to their full alkaloid profile, not to apparicine.

The only figures in the literature are laboratory concentrations, listed here purely so they are not mistaken for doses:

These are assay concentrations from preclinical research. None of them is a dose, and none is a personal recommendation.

References

1. Joule JA, Monteiro H, Durham LJ, Gilbert B, Djerassi C (1965). Alkaloid studies. 48. The structure of apparicine, a novel Aspidosperma alkaloid. Journal of the Chemical Society Perkin 1. https://pubmed.ncbi.nlm.nih.gov/5891947/
2. Farnsworth NR, Fong HH (1969). Identity of pericalline, tabernoschizine, apparicine and gomezine. Journal of Pharmaceutical Sciences. https://pubmed.ncbi.nlm.nih.gov/5779884/
3. Noguchi Y, Hirose T, Ishiyama A, Iwatsuki M, Otoguro K, Sunazuka T, Ōmura S (2016). Synthesis and stereochemical determination of an antiparasitic pseudo-aminal type monoterpene indole alkaloid. Journal of Natural Medicines. https://pubmed.ncbi.nlm.nih.gov/27324906/
4. Bennasar ML, Zulaica E, Solé D, Roca T, García-Díaz D, Alonso S (2009). Total synthesis of the bridged indole alkaloid apparicine. The Journal of Organic Chemistry. https://pubmed.ncbi.nlm.nih.gov/19824689/
5. Bennasar ML, Zulaica E, Solé D, Alonso S (2009). The first total synthesis of (±)-apparicine. Chemical Communications. https://pubmed.ncbi.nlm.nih.gov/19503874/
6. Ingkaninan K, Ijzerman AP, Taesotikul T, Verpoorte R (1999). Isolation of opioid-active compounds from Tabernaemontana pachysiphon leaves. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/10678501/
7. Shi BB, Chen J, Bao MF, Zeng Y, Cai XH (2019). Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activity. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/31302343/
8. Chierrito TP, Aguiar AC, de Andrade IM, Ceravolo IP, Gonçalves RA, de Oliveira AJ, Krettli AU (2014). Anti-malarial activity of indole alkaloids isolated from Aspidosperma olivaceum. Malaria Journal. https://pubmed.ncbi.nlm.nih.gov/24731256/
9. Mai Z, Richardson MB, Mann SGA, Greene J, Paul AA, Perley JO, Deslongchamps G, Qu Y (2025). Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversification. Plant Physiology and Biochemistry. https://pubmed.ncbi.nlm.nih.gov/40168857/
10. Höft M, Verpoorte R, Beck E (1998). Leaf alkaloid contents of Tabernaemontana pachysiphon as influenced by endogenous and environmental factors in the natural habitat. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/17253230/
11. Höft M, Verpoorte R, Beck E (1996). Growth and alkaloid contents in leaves of Tabernaemontana pachysiphon Stapf (Apocynaceae) as influenced by light intensity, water and nutrient supply. Oecologia. https://pubmed.ncbi.nlm.nih.gov/28307301/
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