Apovincamine

Apovincamine at a Glance

Apovincamine is a monoterpenoid indole alkaloid of the eburnamine–vincamine (eburnane) series — the same chemical family that gives lesser periwinkle (Vinca minor) its pharmaceutical reputation. Structurally it is vincamine minus a molecule of water: where vincamine carries a tertiary hydroxyl and an ester side chain, apovincamine has lost the hydroxyl to form a double bond, leaving methyl (3α,16α)-eburnamenine-14-carboxylate, C₂₁H₂₄N₂O₂ ^{23Reference 23National Center for Biotechnology Inform · 2026PubChem Compound Summary for CID 71204, Apovincamine (C21H24N2O2, MW 336.4, CAS 4880-92-6; synonyms include methyl (3α,16α)-eburnamenine-14-carboxylate and Vinpocetine EP impurity B)View study →}.

Its significance is almost entirely positional. Swap apovincamine’s methyl ester for an ethyl ester and you have vinpocetine — sold under the chemical name ethyl apovincaminate — which is one of the most widely used cerebrovascular drugs in Central and Eastern Europe and a contested nootropic supplement elsewhere. Apovincamine is therefore the hinge on which a plant alkaloid becomes a pharmaceutical, and that is the honest reason it matters.

What it is not is a studied molecule in its own right. A PubMed search for apovincamine (July 2026) returns 123 records; exactly one carries the word in its title, and that 1978 paper is an assay for apovincamine acid ethyl ester — vinpocetine again. Restricting to apovincaminate[Title] returns 30 records, every one of them an ester or a synthetic derivative. Apovincamine itself has a single published bioassay result to its name ^{5Reference 5Koyama K et al. · 2010Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophoraView study →}. Everything else here is either chemistry, or a finding that belongs to its relatives and is labelled as such.

The Vincamine → Apovincamine → Vinpocetine Bridge

This is the point of the molecule, so it is worth spelling out precisely.

Step one — vincamine. Vinca minor leaves accumulate vincamine, the plant’s dominant alkaloid and the reason it is farmed for extraction rather than eaten. Chemically vincamine is a hydroxy ester: methyl vincaminate, bearing a tertiary hydroxyl at C-14.

Step two — dehydration to apovincamine. Eliminate that water and the ring system aromatises into the eburnamenine skeleton. The product is apovincamine — the methyl ester of apovincaminic acid. The prefix apo- is doing exactly the work it usually does in alkaloid chemistry: a compound derived from the parent by loss of water.

Step three — transesterification to vinpocetine. Replace the methyl with an ethyl group and you get ethyl apovincaminate, developed at Gedeon Richter as RGH-4405 and marketed as Cavinton — the compound the English-speaking world knows as vinpocetine ^{1,2Reference 1Vas A · 2005Eburnamine derivatives and the brainView study →Reference 2Szatmari SZ · 2003Systematic reviewVinpocetine for cognitive impairment and dementiaView study →}. A Cochrane review states the relationship plainly: vinpocetine is “a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor)” ^{2Reference 2Szatmari SZ · 2003Systematic reviewVinpocetine for cognitive impairment and dementiaView study →}.

The nuance that matters. Apovincamine is a formal intermediate, not necessarily an isolated one. The 1976 synthesis paper that describes the route notes that starting from (+)-vincamine, the water elimination and the esterification can be carried out in one step ^{3Reference 3Lőrincz C et al. · 1976The synthesis of ethyl apovincaminateView study →} — so a plant producing tonnes of vincamine is converted to vinpocetine without ever stockpiling apovincamine. That is a large part of why the molecule has no literature of its own: industrially it is a way-station, and analytically it survives mainly as a pharmacopoeial impurity of vinpocetine (listed as Vinpocetine EP impurity B) ^{23Reference 23National Center for Biotechnology Inform · 2026PubChem Compound Summary for CID 71204, Apovincamine (C21H24N2O2, MW 336.4, CAS 4880-92-6; synonyms include methyl (3α,16α)-eburnamenine-14-carboxylate and Vinpocetine EP impurity B)View study →}.

The chemistry also runs backwards. A 1992 Tetrahedron paper in the long Hungarian “Synthesis of vinca alkaloids” series describes a simple two-step transformation of apovincamine back into vincamine, via a 15α-chloro intermediate ^{4Reference 4Moldvai I et al. · 1992Synthesis of vinca alkaloids and related compounds LXView study →} — useful when the synthetic alkaloid is cheaper than the extracted one.

Three Molecules That Get Confused

Molecule	Relationship to apovincamine	What it actually is
Vincamine	its parent (apovincamine = vincamine − H2O)	the natural V. minor alkaloid; a methyl ester bearing a C-14 hydroxyl
Vinpocetine (ethyl apovincaminate)	its ethyl ester	semi-synthetic; occurs in no plant in normal circumstances; the compound with the clinical record
Apovincaminic acid (AVA, cAVA)	its free acid	vinpocetine’s main circulating metabolite, formed by ester cleavage 11,13Reference 11Szeleczky G · 1986Pharmacokinetic and metabolic studies of vinpocetine on dogsView study →Reference 13Petric Z et al. · 2023Clinical pharmacology of vinpocetine: properties revisited and introduction of a population pharmacokinetic model for its metabolite, apovincaminic acid (AVA)View study →

Two negatives are worth stating alongside them. Vinblastine and vincristine are not in this story at all — those bisindole chemotherapy alkaloids come from Catharanthus roseus (Madagascar periwinkle), a different genus with a different chemistry and a different clinical purpose. And apovincamine is not vinpocetine: a finding about the ethyl ester is not automatically a finding about the methyl ester, because ester identity changes lipophilicity, esterase handling and absorption site — three things this family is demonstrably sensitive to ^{12,21Reference 12Pudleiner P · 1993Study on the absorption of vinpocetine and apovincaminic acidView study →Reference 21Károly M et al. · 2003Lipophilicity of vinpocetine and related compounds characterized by reversed-phase thin-layer chromatographyView study →}.

What It's Used For

The evidence position is unusual and should be read carefully: the class is well studied, the ester is very well studied, and the molecule is almost unstudied.

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. One application is scoreable for this molecule; it is scored low because it rests on a single in-vitro result reported as a secondary finding.

Nothing else here is scoreable. The cerebral-flow, antihypoxic and neuroprotective profile normally attached to the eburnane alkaloids has never been tested on apovincamine as a discrete compound, so it appears below as a labelled class attribution rather than a ranked application. Assigning it a percentage would be borrowing vinpocetine’s evidence base, which is precisely what must be avoided.

01Anti-melanogenesis (skin pigmentation)Shaky18%One in-vitro result in B16 mouse melanoma cells, isolate, reported as a comparator alongside new alkaloids ^{5Reference 5Koyama K et al. · 2010Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophoraView study →}

2. Cerebral Flow, Antihypoxia & Neuroprotection — a Class Attribution, Not a Measurement

This is the profile the molecule is assumed to have, and the reason it appears on the lesser periwinkle mechanism table. The class-level basis is real: a 2005 review of eburnamine derivatives and the brain lists vincamine, vinburnine, vindeburnol, apovincaminate and vinpocetine together as alkaloids that “share modulatory effects on brain circulation and neuronal homeostasis” and “bear antihypoxic and neuroprotective potencies to various degrees” ^{1Reference 1Vas A · 2005Eburnamine derivatives and the brainView study →}.

What the phrase conceals is that the degrees were established for some members and inferred for others. The primary studies behind the class claim are all esters: an acute infusion of vincamine versus ethyl apovincaminate on cerebral blood flow in healthy volunteers ^{14Reference 14Lim CC et al. · 1980Clinical trialThe effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteersView study →}; the hemodynamic comparison of vincamine and apovincaminic acid ethylester (RGH-4405) in dogs, which showed a larger rise in vertebral than femoral flow and was read as cerebral selectivity ^{15Reference 15Caravaggi AM et al. · 1977Hemodynamic profile of a new cerebral vasodilator, vincamine and of one of its derivatives, apovincaminic acid ethylester (RGH-4405)View study →}; and an EEG study in cats where ethyl apovincaminate lengthened cortical resistance time and shortened recovery time under ischaemic anoxia ^{16Reference 16Bíró K et al. · 1976Protective activity of ethyl apovincaminate on ischaemic anoxia of the brainView study →}.

Later work in the series extended it to nitrooxyalkyl and hydroxyethyl apovincaminate esters ^{20Reference 20Nemes A et al. · 2008Synthesis and evaluation of 2’-hydroxyethyl trans-apovincaminate derivatives as antioxidant and cognitive enhancer agentsView study →} — again, esters. Apovincamine, the methyl ester, appears in none of them.

Gap: no study has measured apovincamine’s effect on cerebral blood flow, hypoxia tolerance, neuronal survival or any CNS endpoint. Until one does, this section is a hypothesis inherited from structural neighbours — and the SAR work in this family shows the side-chain ester is not a spectator: changing it changes lipophilicity, metabolic handling and in-vivo potency ^{20,21Reference 20Nemes A et al. · 2008Synthesis and evaluation of 2’-hydroxyethyl trans-apovincaminate derivatives as antioxidant and cognitive enhancer agentsView study →Reference 21Károly M et al. · 2003Lipophilicity of vinpocetine and related compounds characterized by reversed-phase thin-layer chromatographyView study →}.

Mechanisms

The last row is the one to hold onto. Vinpocetine’s characterised targets are frequently written up as “the mechanism of the periwinkle alkaloids”; none of them has been demonstrated for apovincamine.

Pharmacokinetics

There is no pharmacokinetic data for apovincamine. No absorption, oral bioavailability, plasma half-life, distribution or clearance figure for the methyl ester was located in any species.

What can be said is what happens to its immediate relatives, because ester cleavage dominates the whole series. The main route of elimination for vincamine, vinpocetine and the methylenedioxy apovincaminic acid ester is hydrolysis of the ester bond, and elimination is rapid in every species studied ^{10Reference 10Vereczkey L · 1985Pharmacokinetics and metabolism of vincamine and related compoundsView study →}. In rats, ethyl apovincaminate is extensively metabolised and only a small fraction is excreted unchanged; the principal urinary metabolite is apovincaminic acid, produced partly by plasma esterases, with indole-ring hydroxylation and conjugation as secondary routes ^{9Reference 9Vereczkey L · 1976AnimalMetabolism of ethyl apovincaminate in the ratView study →}. Dog studies agree — apovincaminic acid is the prevailing metabolite in both urine and faeces ^{11Reference 11Szeleczky G · 1986Pharmacokinetic and metabolic studies of vinpocetine on dogsView study →} — and a population pharmacokinetic model for apovincaminic acid in humans was published only in 2023, the authors noting how scarce the data still are ^{13Reference 13Petric Z et al. · 2023Clinical pharmacology of vinpocetine: properties revisited and introduction of a population pharmacokinetic model for its metabolite, apovincaminic acid (AVA)View study →}. Absorption is site-dependent within the family: in rat loop experiments the acid is absorbed mainly from the stomach while the ester is absorbed from the small intestine ^{12Reference 12Pudleiner P · 1993Study on the absorption of vinpocetine and apovincaminic acidView study →}, and reversed-phase TLC puts the therapeutically interesting eburnanes across a wide log P range of 2.9–4.8 ^{21Reference 21Károly M et al. · 2003Lipophilicity of vinpocetine and related compounds characterized by reversed-phase thin-layer chromatographyView study →}.

The reasonable inference — and it is only an inference — is that apovincamine would also be hydrolysed to apovincaminic acid, and would behave more like vinpocetine than like the free acid. No study has tested this, so its absolute bioavailability, half-life and the extent of first-pass ester cleavage are all unknown.

Clinical Trials

None. Apovincamine has never entered a clinical trial, and no preclinical development programme for it was located. It has an INN (apovincaminum), which reflects its place in the Gedeon Richter alkaloid programme rather than any clinical career of its own. The trials, the Cochrane review ^{2Reference 2Szatmari SZ · 2003Systematic reviewVinpocetine for cognitive impairment and dementiaView study →} and the decades of Hungarian and Russian cerebrovascular studies all belong to ethyl apovincaminate.

Last checked: July 2026.

Isolate vs. Plant Studies

This molecule sits at an odd extreme of the isolate-versus-plant question: it has neither.

There is no whole-plant study attributing an effect to apovincamine, because no Vinca minor preparation has ever been standardised to it — the herb’s marker is vincamine, and even that is present at well under a tenth of a percent of dry mass ^{6Reference 6Farahanikia B et al. · 2011Phytochemical investigation of Vinca minor cultivated in IranView study →}. And there is essentially no isolate study either: one in-vitro screen ^{5Reference 5Koyama K et al. · 2010Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophoraView study →}, in a paper whose subject was a different plant and eight different alkaloids.

What exists in abundance is a third category the page has to keep separate — evidence for a chemical relative. Ethyl apovincaminate has human cerebral-blood-flow data ^{14Reference 14Lim CC et al. · 1980Clinical trialThe effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteersView study →}, animal hemodynamic and anti-ischaemic data ^{15,16Reference 15Caravaggi AM et al. · 1977Hemodynamic profile of a new cerebral vasodilator, vincamine and of one of its derivatives, apovincaminic acid ethylester (RGH-4405)View study →Reference 16Bíró K et al. · 1976Protective activity of ethyl apovincaminate on ischaemic anoxia of the brainView study →}, a full metabolic map ^{9,11Reference 9Vereczkey L · 1976AnimalMetabolism of ethyl apovincaminate in the ratView study →Reference 11Szeleczky G · 1986Pharmacokinetic and metabolic studies of vinpocetine on dogsView study →}, a modern population PK model for its metabolite ^{13Reference 13Petric Z et al. · 2023Clinical pharmacology of vinpocetine: properties revisited and introduction of a population pharmacokinetic model for its metabolite, apovincaminic acid (AVA)View study →} and a Cochrane review of its dementia trials ^{2Reference 2Szatmari SZ · 2003Systematic reviewVinpocetine for cognitive impairment and dementiaView study →}. None of that is transferable by default. The family’s own SAR literature is the argument against transferring it: a dedicated series of 2′-hydroxyethyl and 2′-acyloxyethyl apovincaminates found that ester structure determined antioxidant and antiamnesic potency strongly enough to single out one member, RGH-10885, as the development candidate ^{20Reference 20Nemes A et al. · 2008Synthesis and evaluation of 2’-hydroxyethyl trans-apovincaminate derivatives as antioxidant and cognitive enhancer agentsView study →}. If swapping ethyl for hydroxyethyl changes the profile that much, swapping ethyl for methyl cannot be assumed to change nothing.

Prevalence in Nature

Apovincamine’s natural occurrence is real but thinly documented, and nowhere quantified.

In lesser periwinkle. The Cochrane review describing vinpocetine’s origin calls apovincamine “a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor)” ^{2Reference 2Szatmari SZ · 2003Systematic reviewVinpocetine for cognitive impairment and dementiaView study →}, which is the clearest statement in the accessible literature that the compound occurs in the plant rather than only in the flask. It is not, however, a compound that modern phytochemical surveys of the species pick up. A phytochemical investigation of cultivated V. minor isolated five indole alkaloids from the aerial parts — vincaminorine, vincaminoreine, minovine, minovincine and vincamine — with vincamine dominant at 0.057% of dried plant mass; apovincamine was not among them ^{6Reference 6Farahanikia B et al. · 2011Phytochemical investigation of Vinca minor cultivated in IranView study →}. A later, much larger isolation from V. minor aerial parts recovered twenty-three compounds and screened them for cholinesterase inhibition without reporting it either ^{7Reference 7Vrabec R et al. · 2022Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): identification of new structural scaffold for treatment of Alzheimer’s diseaseView study →}. The plant’s alkaloid pool is genuinely wide — two promiscuous V. minor cytochrome P450 hydroxylases diversify it across the aspidosperma and akuammiline subclasses ^{8Reference 8Mai Z et al. · 2025Promiscuous and regiospecific Vinca minor hydroxylases for opioid akuammine biosynthesis and monoterpenoid indole alkaloid diversificationView study →} — but apovincamine is a minor member of it at best.

There is also an open question about whether some reported occurrences are artefactual. Vincamine gives up its water readily — readily enough that the industrial route performs the elimination and the esterification in a single pot ^{3Reference 3Lőrincz C et al. · 1976The synthesis of ethyl apovincaminateView study →} — so apovincamine can in principle be generated from the parent alkaloid by the acid or heat of an extraction rather than being present in the living tissue. No study located has tested for it in fresh, unprocessed leaf, so the distinction remains unresolved.

Elsewhere in Apocynaceae. Apovincamine was available as an authentic compound for testing in a study of Alstonia pneumatophora, an Apocynaceae tree of Malaysia, where it was screened alongside the plant’s own new alkaloids ^{5Reference 5Koyama K et al. · 2010Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophoraView study →}. A related curiosity from the same family: ethyl apovincaminate itself — the semi-synthetic ester — was reported among four alkaloids isolated from the stem bark of Tabernaemontana catharinensis ^{22Reference 22Reis FL et al. · 2022In vitroIn vitro antiproliferative activity of alkaloids isolated from Tabernaemontana catharinensis A.DC (Apocynaceae)View study →}. That is a single, isolated claim that runs against the standard position that vinpocetine occurs in no living plant, and it should be treated as unconfirmed rather than as evidence that the drug is a natural product.

No concentration figures. No % dry weight, mg/g, or share-of-alkaloid-fraction has been published for apovincamine in any species or plant part. That is an absence in the literature, not an omission here.

Discovery & Synthesis

Origin. Apovincamine is a product of the mid-twentieth-century European vinca-alkaloid effort rather than a classical isolation with a famous date. Vincamine’s own pharmaceutical career began in the 1950s–60s, and the chemists at Gedeon Richter Ltd. in Budapest systematically derivatised it in the search for a better-behaved cerebroactive compound ^{1Reference 1Vas A · 2005Eburnamine derivatives and the brainView study →}. Apovincamine — the dehydration product — was one of the obvious first stops on that road, and the acid, alcohol and ester family around it (apovincaminic acid, apovincaminol, the alkyl apovincaminates) was mapped out in the same programme.

The landmark paper. In 1976 Lőrincz, Szász and Kisfaludy published The synthesis of ethyl apovincaminate in Arzneimittel-Forschung, describing how, starting from (+)-vincamine, simple derivatives of vincaminic acid, apovincaminic acid and apovincaminol were prepared — and reporting in detail the synthesis of ethyl apovincaminate (Cavinton) as the representative member, with the water elimination and esterification carried out in a single step ^{3Reference 3Lőrincz C et al. · 1976The synthesis of ethyl apovincaminateView study →}. That paper is effectively the birth certificate of vinpocetine, and it is also the clearest statement of apovincamine’s role: a structure on the reaction arrow rather than a product.

Reverse synthesis. The transformation is not one-way. In 1992 Moldvai, Szántay Jr., Rissanen and Szántay published a simple two-step conversion of apovincamine into vincamine via a 15α-chloro intermediate, in part LX of the same Hungarian synthesis series ^{4Reference 4Moldvai I et al. · 1992Synthesis of vinca alkaloids and related compounds LXView study →}.

Manufacture today. Commercial supply of the eburnane drugs starts with vincamine extracted from cultivated Vinca minor, which is then dehydrated and esterified. Apovincamine is not sold as a therapeutic; where it is produced deliberately it is as an analytical reference standard for vinpocetine impurity testing (pharmacopoeial impurity B) or as a synthetic intermediate ^{23Reference 23National Center for Biotechnology Inform · 2026PubChem Compound Summary for CID 71204, Apovincamine (C21H24N2O2, MW 336.4, CAS 4880-92-6; synonyms include methyl (3α,16α)-eburnamenine-14-carboxylate and Vinpocetine EP impurity B)View study →}. There is no market for the methyl ester itself.

Patents: not yet researched.

Toxicity & Safety

No toxicology exists for apovincamine. There is no acute or repeat-dose study, no genotoxicity assay, no reproductive-toxicity study, no interaction study and no human exposure record for the molecule as a discrete compound.

The moderate grading here is therefore a class-inherited precaution, not a measured finding, and it is set deliberately rather than left blank. Three things justify it. First, this is a pharmacologically active alkaloid scaffold, not an inert plant metabolite. Second, the eburnane family carries documented human harms at the parent level — parenteral vincamine has caused ventricular arrhythmias, QT prolongation and torsades de pointes, as the lesser periwinkle monograph sets out. Third, the developmental-toxicity signal in this family is not a fringe concern: the 1976 safety package for ethyl apovincaminate concluded the compound was not teratogenic in rats and rabbits but nonetheless advised against administration in pregnancy ^{17Reference 17Cholnoky E · 1976Summary of safety tests of ethyl apovincaminateView study →}, and modern work is less reassuring — vinpocetine disrupted morphogenesis in mouse and human 3D gastruloids at concentrations in the range used to elicit its purported neuroprotective effects, with its metabolite apovincaminic acid producing similar effects only at substantially higher concentrations ^{19Reference 19Maki A · 2026AnimalDevelopmental toxicity evaluation of the dietary supplement vinpocetine using mouse and human 3D gastruloidsView study →}. The US FDA warns against vinpocetine use by anyone pregnant or who could become pregnant.

That last comparison also cuts the other way and is worth stating fairly: the ester and the acid did not behave identically in the gastruloid assay ^{19Reference 19Maki A · 2026AnimalDevelopmental toxicity evaluation of the dietary supplement vinpocetine using mouse and human 3D gastruloidsView study →}, which is a direct demonstration that toxicity does not transfer automatically across this family either. Apovincamine’s own developmental profile is simply unknown.

Safety at a Glance

⚠️ Moderate toxicityCardiac caution

• No toxicology of its own. Nothing has been tested on apovincamine — the “moderate” flag is inherited from its chemical family, not measured.
• Cardiovascular caution runs in this family. The parent alkaloid vincamine has caused serious ventricular arrhythmias and QT prolongation when given parenterally.
• Developmental-toxicity signal in the relatives. Vinpocetine impairs gastruloid morphogenesis at low micromolar concentrations and carries an FDA warning against use in pregnancy; the 1976 ethyl-apovincaminate safety package likewise advised against use in pregnancy despite finding no teratogenicity.
• Interactions unassessed. No CYP, transporter or protein-binding study of apovincamine exists. Absence of reported interactions here means nobody has looked.

Dosage

There is no dose. Apovincamine has never been administered to a person or an animal as a therapeutic agent in any study located, has no marketed product, and has no research dose range — not even a single in-vivo figure.

The doses that circulate under similar names are not this molecule’s:

These are figures from research on other compounds, reproduced only to show which literature they belong to. They are not a personal recommendation, and they are not a dose for apovincamine.

References

1. Vas A, Gulyás B (2005). Eburnamine derivatives and the brain. Medicinal Research Reviews. https://pubmed.ncbi.nlm.nih.gov/16158388/
2. Szatmari SZ, Whitehouse PJ (2003). Vinpocetine for cognitive impairment and dementia. Cochrane Database of Systematic Reviews (systematic review). https://pubmed.ncbi.nlm.nih.gov/12535455/
3. Lőrincz C, Szász K, Kisfaludy L (1976). The synthesis of ethyl apovincaminate. Arzneimittel-Forschung. https://pubmed.ncbi.nlm.nih.gov/1037211/
4. Moldvai I, Szántay C Jr, Rissanen K, Szántay C (1992). Synthesis of vinca alkaloids and related compounds LX. A simple transformation of apovincamine into vincamine. Tetrahedron. https://doi.org/10.1016/S0040-4020(01)81593-3
5. Koyama K, Hirasawa Y, Hosoya T, Hoe TC, Chan KL, Morita H (2010). Alpneumines A-H, new anti-melanogenic indole alkaloids from Alstonia pneumatophora. Bioorganic & Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/20576577/
6. Farahanikia B, Akbarzadeh T, Jahangirzadeh A, Yassa N, Shams Ardekani MR, Mirnezami T, Hadjiakhoondi A, Khanavi M (2011). Phytochemical investigation of Vinca minor cultivated in Iran. Iranian Journal of Pharmaceutical Research. https://pubmed.ncbi.nlm.nih.gov/24250413/
7. Vrabec R, Maříková J, Ločárek M, et al. (2022). Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): identification of new structural scaffold for treatment of Alzheimer’s disease. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/34798410/
8. Mai Z, Richardson MB, Mann SGA, et al. (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/
9. Vereczkey L, Szporny L (1976). Metabolism of ethyl apovincaminate in the rat. Arzneimittel-Forschung. https://pubmed.ncbi.nlm.nih.gov/1037219/
10. Vereczkey L (1985). Pharmacokinetics and metabolism of vincamine and related compounds. European Journal of Drug Metabolism and Pharmacokinetics. https://pubmed.ncbi.nlm.nih.gov/3899662/
11. Szeleczky G, Vereczkey L (1986). Pharmacokinetic and metabolic studies of vinpocetine on dogs. II. Metabolism. Polish Journal of Pharmacology and Pharmacy. https://pubmed.ncbi.nlm.nih.gov/3774625/
12. Pudleiner P, Vereczkey L (1993). Study on the absorption of vinpocetine and apovincaminic acid. European Journal of Drug Metabolism and Pharmacokinetics. https://pubmed.ncbi.nlm.nih.gov/8020528/
13. Petric Z, Paixão P, Filipe A, Guimarães Morais J (2023). Clinical pharmacology of vinpocetine: properties revisited and introduction of a population pharmacokinetic model for its metabolite, apovincaminic acid (AVA). Pharmaceutics. https://pubmed.ncbi.nlm.nih.gov/37896263/
14. Lim CC, Cook PJ, James IM (1980). The effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteers. British Journal of Clinical Pharmacology (clinical trial). https://pubmed.ncbi.nlm.nih.gov/7356869/
15. Caravaggi AM, Sardi A, Baldoli E, Di Francesco GF, Luca TC (1977). Hemodynamic profile of a new cerebral vasodilator, vincamine and of one of its derivatives, apovincaminic acid ethylester (RGH-4405). Archives Internationales de Pharmacodynamie et de Thérapie. https://pubmed.ncbi.nlm.nih.gov/869636/
16. Bíró K, Kárpáti E, Szporny L (1976). Protective activity of ethyl apovincaminate on ischaemic anoxia of the brain. Arzneimittel-Forschung. https://pubmed.ncbi.nlm.nih.gov/1037215/
17. Cholnoky E, Dömök LI (1976). Summary of safety tests of ethyl apovincaminate. Arzneimittel-Forschung. https://pubmed.ncbi.nlm.nih.gov/1037220/
18. Nyakas C, Felszeghy K, Szabó R, Keijser JN, Luiten PG, Szombathelyi Z, Tihanyi K (2009). Neuroprotective effects of vinpocetine and its major metabolite cis-apovincaminic acid on NMDA-induced neurotoxicity in a rat entorhinal cortex lesion model. CNS Neuroscience & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/19492990/
19. Maki A, Marikawa Y (2026). Developmental toxicity evaluation of the dietary supplement vinpocetine using mouse and human 3D gastruloids. Birth Defects Research. https://pubmed.ncbi.nlm.nih.gov/42167926/
20. Nemes A, Czibula L, Szántay C Jr, Gere A, Kiss B, Laszy J, Gyertyán I, Szombathelyi Z, Szántay C (2008). Synthesis and evaluation of 2’-hydroxyethyl trans-apovincaminate derivatives as antioxidant and cognitive enhancer agents. Journal of Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/18183943/
21. Károly M, Vámos J, Nemes A, Rácz A, Noszál B (2003). Lipophilicity of vinpocetine and related compounds characterized by reversed-phase thin-layer chromatography. Journal of Chromatography A. https://pubmed.ncbi.nlm.nih.gov/12830921/
22. Reis FL, Adolpho L, Ruiz ALTG, Simionatto E, Dalcol II, Mostardeiro MA, Morel AF (2022). In vitro antiproliferative activity of alkaloids isolated from Tabernaemontana catharinensis A.DC (Apocynaceae). Natural Product Research. https://pubmed.ncbi.nlm.nih.gov/35075954/
23. National Center for Biotechnology Information. PubChem Compound Summary for CID 71204, Apovincamine (C₂₁H₂₄N₂O₂, MW 336.4, CAS 4880-92-6; synonyms include methyl (3α,16α)-eburnamenine-14-carboxylate and Vinpocetine EP impurity B). Accessed July 2026. https://pubchem.ncbi.nlm.nih.gov/compound/71204

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