Vinburnine

Other Names

(-)-Eburnamonina(15S,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18)-tetraen-17-one(3alpha,16alpha)-14,15-Dihydroeburnamenin-14-one(3alpha,16alpha)-Eburnamenin-14(15H)-one14,15-Dihydroeburnamenin-14-one16-Oxoeburnane3-alpha,16-alpha-Eburnamonine3alpha,16alpha-EburnamonineCervoxanCH-846cis-VincamoneDL-EburnamonineEburnalEburnamenin-14(15H)-oneEburnamonineEburnamonine (-)-formEburnamonine, (3alpha,16alpha)-isomerL-EburnamonineNSC-322920VinburninaVincamonaVincamoneVincanorine

Synopsis

Vinburnine (Eburnamonine / Vincamone)

Identity, Nomenclature, and Natural Source

The three names vinburnine, (−)-eburnamonine, and (−)-vincamone refer to the same product. Vinburnine (also called eburnamonine or vincamone) is a vasodilator and a vinca alkaloid that is a metabolite of vincamine. Structurally, vinburnine belongs to the eburnamine–vincamine class of indole alkaloids, all of which share a characteristic pentacyclic ring skeleton derived from the eburnane core.

The racemate of the alkaloid vinburnine is known as (±)-eburnamonine. Dextrorotatory, levorotatory, and racemic forms of eburnamonine exist in nature. The (−)-form, also known as vincamone and isolated from Vinca minor, is the form used pharmaceutically; it possesses stimulating activity for muscle and is used as a cerebrotonic, whereas both enantiomers have hypotensive effects.

The primary botanical source of vinburnine is Vinca minor L. (lesser periwinkle), a member of the family Apocynaceae. Vinca minor, commonly known as lesser periwinkle or dwarf periwinkle, is a species of flowering plant in the dogbane family, native to central and southern Europe; other names used in cultivation include small periwinkle, common periwinkle, and sometimes in the United States, myrtle or creeping myrtle. This plant is native to northern Spain, western France, central and southern Europe, and the Caucasus.

The Apocynaceae plants are the sources of a number of eburnamine–vincamine alkaloids such as vincamine, vinburnine, vindeburnol, apovincaminate, and vinpocetine that are known to modulate various brain functions. Vinca minor contains monomeric eburnamine-type indole alkaloids including vincamine, which has modulatory effects on brain circulation and neuronal homeostasis as well as antihypoxic and neuroprotective potencies. More than 50 alkaloids of indole type have been isolated from the aerial parts and the root of this plant.

After extensive structural modifications, three derivatives of vincamine have been developed as cerebral vasodilators used to treat brain disorders, based on their beneficial properties on brain circulation and neuronal homeostasis. These include (+)-brovincamine (11-bromovincamine or sabromine), (−)-eburnamonine (cervoxane, vinburnine, or vincamone), and (+)-vinpocetine (ethyl apovincaminate or Cavinton®). The trade names cervoxane and vincamone have been associated with the compound in various European markets.

The CAS Registry Number of (−)-vinburnine is 4880-88-0. The IUPAC systematic name is (41S,13aS)-13a-ethyl-2,3,5,6,13,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridin-12(41H)-one. Vinca alkaloids are now produced synthetically and used as drugs; additional researched vinca alkaloids alongside the well-known anticancer agents include vincaminol, vineridine, and vinburnine.

Common Forms and Preparations

Vinburnine has been formulated in several pharmaceutical preparations. Peer-reviewed pharmaceutical studies from the late 1980s document both oral solid and oral liquid dosage forms. An oral liquid form of vinburnine was studied biopharmaceutically (Sado et al., J Pharm Belg. 1989 Jan–Feb;44(1):50–59). Separately, the effect of modification of excipients on the bioavailability of vinburnine was also investigated (Sado et al., J Pharm Belg. 1989 May–Jun;44(3):221–229), indicating that oral bioavailability is formulation-sensitive. Intravenous infusion has been used in clinical pharmacological investigations. In one in vivo study, 40 mg of vinburnine was infused in a systemic vein to evaluate effects on blood rheology, oxygen transport, and regional circulation. As a dietary supplement, the compound is available in capsule or tablet form in some markets, typically containing the isolated (−)-enantiomer.

Historical and Traditional Use

The history of vinburnine as a distinct chemical entity is relatively modern, but it is inseparable from the long ethnomedicinal history of its parent plant, Vinca minor. Periwinkle has likely been used for medicine for a long time; its Latin name, Vinca, is derived from the Latin word vincere, meaning "to overcome." European herbalists have used periwinkle for headaches, vertigo, and poor memory since medieval times. It was also considered a helpful remedy for conditions with a watery or bloody discharge such as diarrhea, bleeding gums, or menorrhagia.

The common or lesser periwinkle (Vinca minor) is a flowering plant native to Europe and northwestern Africa and was introduced in the US as a medicinal herb and ornamental ground cover. Vinca minor has been used in folk medicine for conditions of the heart, nervous system, gastrointestinal system, and menstruation, and is commonly used to improve "brain health" and memory.

In France, periwinkle was regarded as a symbol of friendship, and if the plant was placed in a buttonhole it was thought to keep evil spirits away. The astringent effect of periwinkle could be exploited by using extracts of the leaves externally as a mouthwash or gargle for sore throat, gingivitis, and mouth ulcers, and as wet compresses to treat minor skin inflammations, eczema, vaginal discharge, and wounds. The herb has also been used to halt nosebleeds by placing the leaves directly into the nostrils.

Historically, the story of these alkaloids traces back to the first isolation of vincamine from the Vinca minor plant by Zabolotnaya, and its structural elucidation in the 1950s. In 1953, vincamine was identified as the main active ingredient in periwinkle and soon after the chemical structure of the substance was mapped; since then, all pharmacological and clinical research done on periwinkle has focused on this isolated substance. Vinburnine itself was subsequently identified as a natural metabolite of vincamine. The oxygen blood supply, the oxygen extraction coefficient, and cerebral oxygen consumption all increased with (−)-eburnamonine treatment, while they decreased when using vincamine; thus, (−)-eburnamonine was launched in 1977 by SmithKline Beecham as a cerebral vasodilator.

Key Constituents and Chemical Classification

Vinburnine is itself a single chemical entity, not a crude herbal extract, and therefore its phytochemical discussion centers on its structural class and biosynthetic relationships.

The Apocynaceae plant family contains a great number of so-called eburnamine–vincamine alkaloids. Quite a few of these alkaloids exert varied pharmacological activities on cell multiplication, the cardiovascular system, and brain functions. Several eburnane alkaloids display vasorelaxation/vasodilating activity, dependent on their enantiomeric configurations. There are many indole alkaloids in the eburnamine–vincamine series — sometimes with closely related names such as eburnamonine, eburnamenine, and eburnamine — and multiple enantiomers exist.

The alkaloids eburnamine from Hunteria eburnea Pichon and vincamine from Vinca minor are the prototypes of the indole alkaloid class eburnamine–vincamine. The alkaloids of this class are derivatives of ring skeletons of the same constitution; the absolute configurations of alkaloids belonging to this series have been established and progress has been made in clarifying their relative and absolute stereochemistry.

The genus Vinca L. (Apocynaceae) is renowned for its rich content of monoterpene indole alkaloids and widespread occurrence in Europe, northwest Africa, and southwest Asia. Extensive phytochemical and pharmacological research has identified 202 alkaloids across five phytochemically investigated Vinca species, categorized into 20 structural groups.

Mechanisms of Action

Cerebrovascular and Vasodilatory Effects

Vinburnine is a peripheral vasodilator with cerebral activities that also acts as a cerebral metabolic stimulant and appears to be able to relax the smooth muscle cells within the walls of blood vessels. This vasodilatory action is considered the primary mechanism underlying its effects on cerebral blood flow and oxygen delivery.

Vincamine, vinburnine, vindeburnol, apovincaminate, and vinpocetine all share modulatory effects on brain circulation and neuronal homeostasis and bear antihypoxic and neuroprotective potencies to various degrees. The Apocynaceae plant family contains a great number of so-called eburnamine–vincamine alkaloids, quite a few of which exert varied pharmacological activities on cell multiplication, the cardiovascular system, and brain functions.

A key differentiating finding between vinburnine and its parent compound vincamine concerns their contrasting effects on cerebral oxygen metabolism: the oxygen blood supply, the oxygen extraction coefficient, and cerebral oxygen consumption all increased with (−)-eburnamonine treatment, while they decreased when using vincamine. This pharmacological distinction was central to the rationale for the development of vinburnine as a separate pharmaceutical agent.

Phosphodiesterase Inhibition

The most eminent compound of this class of alkaloids is vinpocetine. Since its introduction to the market as a neuroprotective agent, many nonclinical and clinical studies proved vinpocetine's effects on calmodulin-dependent phosphodiesterase E1, on sodium, calcium channels, peripheral benzodiazepine receptor, and glutamate receptors. Vinburnine shares structural and pharmacological features with vinpocetine within the eburnamine series, and phosphodiesterase inhibition has been proposed as a contributing mechanism for the broader class, though specific PDE inhibition data for vinburnine itself remain limited in the published peer-reviewed literature.

Allosteric Modulation of Muscarinic Acetylcholine Receptors

An important and well-characterized mechanism for vinburnine involves its interaction with muscarinic acetylcholine receptors. The kinetics of [³H]N-methylscopolamine binding to membranes of Chinese hamster ovary (CHO) cells expressing muscarinic M(1)–M(4) acetylcholine receptors was studied. [³H]N-methylscopolamine dissociation was used for the analysis of allosteric modulation by vinburnine (L-eburnamonine). The dissociation was decelerated by vinburnine with EC₅₀ values of 29.5, 4.1, 9.5, and 15.0 µM for muscarinic M(1)–M(4) receptors, respectively. Acetylcholine doubled the EC₅₀ of vinburnine for muscarinic M(3) receptors. These kinetic EC₅₀ values correlated with equilibrium binding constants, supporting the ternary allosteric model. Vinburnine also decelerated the association of [³H]N-methylscopolamine binding, resulting in opposite cooperativity for muscarinic M(1) and M(2) receptors.

This allosteric muscarinic receptor modulation has been further examined in cardiac tissue. Alcuronium and strychnine allosterically increase the affinity of cardiac muscarinic receptors for the antagonist N-methylscopolamine. In experiments on rat heart atria, l-eburnamonine was found to increase the binding of [³H]N-methylscopolamine with Ehlert's cooperativity coefficient α = 0.35, indicating that the strength of its allosteric action is close to that of alcuronium and strychnine (α = 0.31 and 0.44, respectively). However, the affinity of l-eburnamonine for the cardiac muscarinic receptors is lower than the affinities of alcuronium and strychnine (KAR = 22.6 µM, 0.15 µM, and 3.4 µM, respectively). In spite of its extremely close structural similarity to l-eburnamonine, vincamine has a negative allosteric effect on the same receptor.

Blood Rheology and Oxygen Transport

Investigations into vinburnine's protective action on blood haemorheology and metabolic parameters showed that in each sample, blood viscosity and filterability, p50 and 2,3-DPG were measured. Vinburnine was able to induce a slight improvement of haemorheological parameters and of p50 compared to controls. After incubation for 4 hours, a reduced impairment of the measured parameters was observed in comparison with controls.

BBB Transport and Metabolic Stability

Vincamine, vinpocetine, and eburnamonine are alkaloids known for their neuroprotective attributes, enhancement of cerebrovascular blood flow, and antitumor effect of their derivatives; however, the relative metabolic stability of these alkaloids and their extrusion by the drug efflux transporters expressed at the blood–brain barrier (BBB) are not fully characterized. Vincamine, vinpocetine, and eburnamonine at 4, 20, and 100 µM displayed minimal interaction with the P-gp and Bcrp drug efflux transporters needed to cross the BBB. This finding suggests that vinburnine is not substantially extruded by the major ABC transporter-based efflux systems at the BBB, which would be consistent with its capacity to exert central nervous system effects.

Scientific Evidence by Area of Use

1. Cerebrovascular Disorders

The most directly investigated clinical application of vinburnine is in cerebrovascular insufficiency. The pivotal human clinical trial was published in Pharmacopsychiatry (1986). Two double-blind, placebo-controlled studies were performed successively to demonstrate the efficacy of eburnamonine. In the first study, the efficacy of 12 weeks of administration of 3 × 60 mg eburnamonine per day (n = 25) was investigated in 49 inpatients with cerebrovascular disorders. In the second, the effect of 12 weeks of therapy with 1 × 60 mg eburnamonine per day (n = 25) was investigated in 50 patients of the same diagnostic category. Results related to efficacy were analyzed on the basis of the physician's global rating of therapeutic effect. Global therapeutic effect was confirmed and illustrated by effects on specific variables (List of Cerebral Symptoms, function test, NOSIE); under the influence of both dosages, therapeutic improvement was observed more frequently than under placebo.

Evidence characterization: These two double-blind, placebo-controlled trials represent the highest level of direct clinical evidence for vinburnine in cerebrovascular disorders. However, the sample sizes were modest (approximately 25 patients per active arm), the primary outcome was a physician's global clinical rating rather than validated neurological endpoints by current standards, and both studies are now several decades old. No large-scale, multi-center randomized controlled trials have been identified in the peer-reviewed literature.

2. Blood Rheology and Peripheral Vascular Effects

Several studies have examined vinburnine's effects on hemorheology and tissue oxygenation. Vinburnine has been shown to be effective in avoiding chronic ischaemic tissue injury, and many studies have demonstrated the antihypoxic and oxygenation properties of this drug.

In one in vivo clinical pharmacological study, a pharmacoclinical study evaluating vinburnine versus placebo studied hemodynamic, microcirculatory, and rheological effects. In the study, the effects on blood rheology, oxygen transport, regional circulation, and ergospirometric data of 40 mg vinburnine infused intravenously were evaluated in two groups: the first group included 10 patients with low hemoglobin oxygen affinity (p50 28.6 ± 1.37 mmHg), and the second included 7 patients with normal values (p50 26.6 ± 0.84 mmHg). Parameters measured included nutritional blood flow, blood gas analysis in arterial and venous blood, hemoglobin oxygen affinity expressed as p50, erythrocytic 2,3-DPG, hemorheological, and ergospirometric parameters. The improvement of rheological properties, hemodynamic and metabolic data in the two groups of the study seemed to confirm the oxyphoretic properties of this drug.

A separate clinical pharmacological study examined vinburnine's hemodynamic, microcirculatory, and rheological effects specifically in angiopathy of the lower limbs in diabetes mellitus (Le Devehat C, Vimeux M. Int Angiol. 1989;8:57–61), as cited in the 2005 Medicinal Research Reviews article by Vas and Gulyás.

Evidence characterization: The hemorheological studies are predominantly small-scale in vivo pharmacological investigations, many published in Italian or French-language journals in the late 1980s to early 1990s. They demonstrate measurable effects on blood viscosity, oxygen transport, and p50, but the clinical significance relative to patient-oriented outcomes has not been established in large trials.

3. Learning, Memory, and Cognitive Effects

Animal experimental evidence for vinburnine's effects on learning and memory was generated primarily using rodent models. Retrograde amnesia was induced experimentally in mice by injecting them with scopolamine (3 mg/kg, IP) or by inducing seizures with pentylenetetrazol (50 mg/kg, IP), and in rats by subjecting them to hypobaric hypoxia (at a barometric pressure of 300 mmHg for 3 min). The effects of vinburnine (VNB) in these amnesic states were compared to vincamine (VNC) and nicergoline (NCG). Vinburnine reduced the disrupting effect of both scopolamine and pentylenetetrazol-induced seizures on the retention of a step-through passive avoidance behavior in mice and on the acquisition of shuttle-box active avoidance behavior in rats. This effect was dose-related up to 20 mg/kg (the peak effect dose after IP administration) and was more pronounced than that of VNC and NCG in some tests.

The muscarinic allosteric modulation documented in vitro (see Mechanisms section) provides a plausible mechanistic basis for the pro-cognitive and anti-amnesic actions observed in animal models. The M1 muscarinic receptor subtype in particular plays a central role in memory consolidation.

Evidence characterization: Evidence for cognitive effects is preclinical only (animal models and in vitro pharmacology). No published randomized controlled human clinical trials specifically examining vinburnine's effects on cognition or memory have been identified in the peer-reviewed literature. Extrapolation from the cerebrovascular disorder clinical trials to cognitive benefit is indirect.

4. Oncology — Melanoma and Immunotherapy Potentiation

A significant and comparatively recent area of vinburnine research concerns its potential as an oncological agent, specifically in the context of melanoma immunotherapy. Melanoma is a highly aggressive and immunogenic skin cancer that often develops resistance to immunotherapy due to the immunosuppressive tumor microenvironment (TME). Although PD-1/PD-L1 inhibitors have significantly improved treatment outcomes, 30%–40% of patients exhibit no response or develop resistance.

A 2025 study evaluated the effects of vinburnine on melanoma cell proliferation, migration, invasion, apoptosis, and DNA damage through in vitro experiments. Transcriptomic analysis, Western blot, RT-PCR, dual-luciferase reporter assays, and ChIP experiments revealed the mechanism by which vinburnine regulates IL-24 via ATF3. The anti-tumor efficacy of vinburnine or IL-24 in combination with a PD-1 monoclonal antibody, as well as their modulation of the tumor microenvironment, were validated through luciferase-mediated cytotoxicity assays and a murine melanoma model. Additionally, the correlation between IL-24 expression and patient prognosis or immunotherapy response was analyzed using public databases.

The study delineated the phenotypic mechanisms by which vinburnine suppresses melanoma proliferation. Vinburnine induces reactive oxygen species (ROS) generation, leading to DNA damage and the subsequent activation of the apoptotic cascade in melanoma cells. Additionally, vinburnine activates the P38/MAPK/ATF3 signaling axis, which drives the secretion of interleukin-24 (IL-24), enhancing the functionality of CD8⁺ T cells and modulating the tumor immune microenvironment to favor antitumor immunity. Notably, the combination of vinburnine with anti-PD-1 antibody therapy produces synergistic effects, effectively addressing certain limitations of current immunotherapeutic approaches.

Evidence characterization: This oncological research (Zhu et al., Journal of Experimental & Clinical Cancer Research, 2025) is entirely preclinical — comprising in vitro cell-line experiments and a murine xenograft model. No human clinical trial data exist for vinburnine in oncology. The findings are hypothesis-generating and represent an emerging line of mechanistic inquiry rather than established clinical evidence.

Body Systems and Health Areas

Central nervous system / Cerebrovascular system: Vincamine, vinburnine, vindeburnol, apovincaminate, and vinpocetine all share modulatory effects on brain circulation and neuronal homeostasis, and bear antihypoxic and neuroprotective potencies to various degrees.
Cardiovascular system / Blood rheology: Vinburnine is a peripheral vasodilator with cerebral activities that also acts as a cerebral metabolic stimulant and appears to be able to relax the smooth muscle cells within the walls of blood vessels.
Cholinergic / Muscarinic system: As documented in CHO cell and cardiac atrial experiments (Maksay et al., 2004; Maksay et al., Eur J Pharmacol. 1996), vinburnine acts as an allosteric modulator at muscarinic M1–M4 receptors.
Immune / Oncological system (preclinical): Vinburnine activates the P38/MAPK/ATF3 signaling axis, which drives the secretion of interleukin-24 (IL-24), enhancing the functionality of CD8⁺ T cells and modulating the tumor immune microenvironment to favor antitumor immunity.

Dosage Forms and Reported Dosages

The following dosages are reported directly from peer-reviewed sources; they reflect investigational or historical pharmaceutical use and should not be interpreted as prescriptive recommendations.

Oral, cerebrovascular disorder clinical trial (Jansen et al., 1986): In the first double-blind study, 3 × 60 mg eburnamonine per day (total 180 mg/day) was administered to inpatients with cerebrovascular disorders over 12 weeks (n = 25). In the second study, 1 × 60 mg eburnamonine per day was administered over 12 weeks (n = 25).
Intravenous, clinical pharmacological study (Domini et al., 1990): 40 mg vinburnine was infused into a systemic vein to evaluate effects on blood rheology, oxygen transport, and regional circulation.
Animal study (Drago et al., 1990): The anti-amnesic effect of vinburnine was dose-related up to 20 mg/kg, which was the peak effect dose after intraperitoneal administration in rodents.
NCATS Inxight Drugs database notation: The recommended dosage cited is 60 mg taken twice a day. (Source: NCATS Inxight Drugs, citing published literature.)

Safety Considerations and Adverse Effects

Hypotensive Effects

Dextrorotatory, levorotatory, and racemic forms of eburnamonine exist in nature. The (−)-form is used as a cerebrotonic, whereas both enantiomers have hypotensive effects. This hypotensive activity is consistent with the compound's mechanism as a peripheral and cerebral vasodilator, and is a pharmacologically predictable effect shared by both optical forms of the molecule.

Cutaneous Adverse Effects — Bullous Fixed Drug Eruption

A clinically significant adverse event documented in the peer-reviewed literature is a bullous fixed drug eruption. A published case report documented a bullous fixed drug eruption induced by vinburnine (Schena D, Menegazzi S, Barba A. Contact Dermatitis. 1992 Sep;27(3):187. PMID: 1451466). This case has subsequently been cited in the dermatological literature as an established precedent for vinburnine as a causative agent for this type of cutaneous drug reaction. The citation, Schena D, Menegazzi S, Barba A — "Bullous fixed drug eruption induced by vinburnine" — appears in Contact Dermatitis 1992;27:187, and is referenced within the broader fixed drug eruption literature.

Drug Efflux Transporter Interactions (In Vitro)

At different concentrations (4, 20, and 100 µM), vincamine, vinpocetine, and eburnamonine (vinburnine) induced minimal stimulation of the ATPase activity of the Bcrp and Pgp membrane transporters. This in vitro finding suggests that at concentrations within a pharmacologically relevant range, vinburnine does not substantially stimulate major drug efflux pumps, which has implications for drug–drug interaction potential at the BBB. However, in vitro transporter data do not directly predict in vivo interactions.

Immunosuppressive Potential (Whole-Plant Context)

The German Commission E has noted that some animal studies suggest periwinkle as a whole plant could suppress the immune system. This warning applies to the crude plant material and its full alkaloid complement rather than to isolated vinburnine specifically, but it is relevant contextual safety information given the shared botanical origin.

Metabolic Stability Considerations

A review of the pharmacokinetics and metabolism of vincamine, vinpocetine, methylene-methoxy-apovincaminic acid ester, and eburnamine indicated that vincamine and its derivatives showed significant differences in metabolic pathways and their elimination was rapid in the species studied. Emphasis has been placed on the analytical methods used for monitoring these drugs in biological systems. The relative metabolic stability of eburnamonine compared to other alkaloids in this series has been investigated in vitro (Fandy et al., 2016), supporting the assessment that it does not undergo the same rapid ester-hydrolysis pathways as vincamine.

General Class Considerations

Many derivatives of the eburnamine–vincamine class were synthesized to find pharmacologically active compounds better characterized and safer to be administered than the natural plant alkaloids themselves, indicating that the safety and tolerability profile of the natural alkaloids was a recognized limiting factor in this class. Vinburnine's development as a pharmaceutical agent was partly driven by this consideration.

Summary of Evidence Strength

The evidence base for vinburnine can be summarized as follows:

Cerebrovascular insufficiency: Two small double-blind, placebo-controlled clinical trials (total n ≈ 100 patients, 12-week duration each) from 1986 showing benefit versus placebo. Evidence is positive but methodologically limited by age, small sample sizes, and soft endpoints. No modern large-scale RCTs have been identified.
Hemorheological and oxygen transport effects: Several small in vivo clinical pharmacological studies (predominantly Italian-language) supporting measurable effects on blood viscosity, p50, and oxygen transport. Clinical relevance in terms of hard endpoints is not established.
Cognitive/memory effects: Preclinical only (rodent models). In vitro muscarinic receptor allosteric modulation documented in CHO cells and cardiac atrial preparations. No published human clinical trials identified.
Oncology (melanoma): Preclinical only (in vitro and murine models, 2025). Hypothesis-generating; no human data.

References

Health Conditions

Health conditions that Vinburnine may help support.

No conditions available.

Body Systems

Body systems that Vinburnine may help support.

No body systems available.