| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
- Muscarinic M1, M2, M3, M4 Acetylcholine Receptors: Vinburnine acts as an allosteric modulator, decelerating the dissociation of [³H]N-methylscopolamine. EC50 values for decelerating dissociation are 29.5 μM (M1), 4.1 μM (M2), 9.5 μM (M3), and 15.0 μM (M4). [1]
- Voltage-gated Sodium Channels: Vinburnine is suggested to block voltage-gated sodium channels, contributing to its neuroprotective effects. [2] |
|---|---|
| ln Vitro |
- Muscarinic Receptor Binding Kinetics: Vinburnine decelerated the dissociation of [³H]N-methylscopolamine from recombinant human muscarinic M1-M4 receptors in a concentration-dependent manner, approaching a maximum at complete inhibition. The EC50 values were 29.5 μM (M1), 4.1 μM (M2), 9.5 μM (M3), and 15.0 μM (M4). The slope values for the Hill equation were higher than unity for M1 and M2 receptors, and close to unity for M3 and M4 receptors. Vinburnine (10-30 μM) also decelerated the association of [³H]N-methylscopolamine binding. For M1 receptors, 30 μM vinburnine decreased the association rate constant (kon) from 0.60 to 0.25 (min·mM)⁻¹. For M2 receptors, 50 μM vinburnine decelerated association to 24% of control (kon decreased from 0.477 to 0.117 (min·mM)⁻¹). [1]
- Red Blood Cell Metabolism: Vinburnine stimulated the glycolysis of red cells in healthy volunteers, leading to increases in red blood cell ATP and 2,3-diphosphoglycerate contents, suggesting increased red blood cell deformability. [2] |
| ln Vivo |
- Cerebral Hemodynamics and Metabolism in Dogs: In anesthetized dogs, intravenous injection of vinburnine (2 mg/kg) increased vertebral, carotid, and femoral blood flows, while corresponding resistances decreased. Aortic blood flow and systolic ejection volume also increased. Cerebral oxygen and glucose consumption increased, as did the oxygen extraction coefficient and oxygen supply. At a higher dose (1 mg/kg/min for 10 min slow i.v. perfusion), vinburnine left vertebral and femoral blood flow unchanged, but increased oxygen blood supply, oxygen extraction coefficient, and cerebral oxygen consumption. [2]
- Cerebral Edema in Rats: In a rat model of triethyltin chloride (TET)-induced cerebral edema, vinburnine (2 x 50 mg/kg/day orally) was effective in ameliorating TET's effects on water content and clinical behavior in different brain regions. [2] - Amnesia Models in Mice and Rats: In mice, vinburnine (5, 10, 20, 50 mg/kg, i.p.) dose-dependently reduced the disrupting effect of scopolamine (3 mg/kg, i.p.) and pentylenetetrazol (50 mg/kg, i.p.)-induced seizures on the retention of a step-through passive avoidance task. The peak effect was at 20 mg/kg. For scopolamine-induced amnesia, the median latencies were 50.0 sec (control), 6.5 sec (scopolamine+vehicle), and 52.0 sec (scopolamine+20 mg/kg vinburnine). For pentylenetetrazol-induced amnesia, median latencies were 46.0 sec (control), 10.0 sec (pentylenetetrazol+vehicle), and 52.0 sec (pentylenetetrazol+20 mg/kg vinburnine). In rats exposed to hypobaric hypoxia (300 mmHg for 3 min), vinburnine (5, 10, 20, 50 mg/kg, i.p.) dose-dependently antagonized the decrease in the acquisition of shuttle-box active avoidance (measured by conditioned avoidance responses, CARs, and percentage of learners) and the retention of passive avoidance behavior. At 20 mg/kg, vinburnine restored CARs to 11.0 ± 0.9 (vs. 4.6 ± 0.1 for hypoxia+vehicle and 12.6 ± 0.5 for controls) and passive avoidance latency to 68.0 sec (vs. 19.5 sec for hypoxia+vehicle and 62.0 sec for controls). [3] |
| Enzyme Assay |
- Muscarinic Receptor Binding Kinetics (Dissociation): Receptor suspensions (expressing human M1-M4 receptors) were diluted in incubation buffer (20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, pH 7.4) and incubated with [³H]N-methylscopolamine (10-20 nM) at 27°C (M1, M3, M4) or 19°C (M2). After total binding was determined, 20-μl aliquots were diluted 100-fold with incubation buffer containing 10 μM NMS to elicit dissociation. Dissociation was monitored for up to 20 minutes in the presence of different concentrations of vinburnine. Dissociation was terminated via filtration. Data were analyzed by fitting to the Hill equation to determine EC50 for deceleration of dissociation. [1]
- Muscarinic Receptor Binding Kinetics (Association): Receptor suspensions were preincubated with or without vinburnine (10-30 μM) and then with 0.3 nM [³H]N-methylscopolamine. 1-ml aliquots were filtered after up to 2 hours of association. Apparent rate constants of association (kapp) were determined by fitting an equation with one exponential. The association rate constant (kon) was calculated using the equation: kapp = ck_on + k_off, where c is the concentration of [³H]NMS. [1] |
| Animal Protocol |
- General: Male rats (Wistar, 160±20 g) and male mice (CD-1, 20±5 g) were used. Animals were housed with food and water ad libitum on a 12-hr light/dark cycle at 21°C. [3]
- Drug Administration (Drago et al., 1990): Vinburnine, vincamine, and nicergoline were dissolved in 1% ascorbic acid or 0.5% tartaric acid, neutralized with NaOH, and diluted with physiological saline. All drugs were administered intraperitoneally (i.p.) at doses of 5, 10, and 20 mg/kg. For vinburnine, a 50 mg/kg dose was also used. Control animals received vehicle alone. Scopolamine HBr (3 mg/kg) and pentylenetetrazol (50 mg/kg) were dissolved in saline and administered i.p. For the hypobaric hypoxia model, rats were exposed to a barometric pressure of 300 mmHg for 3 minutes in a hypobaric chamber. [3] - Behavioral Tests (Mice - Passive Avoidance): Mice were adapted to a two-compartment apparatus (a large dark compartment with a grid floor and an elevated lighted runway). After adaptation, they received a single footshock (0.25 mA AC for 2 sec) upon entering the dark box. Retention was tested 24 hours later by measuring the latency to re-enter the dark compartment (max 300 sec). For scopolamine-induced amnesia, scopolamine was injected 1 hr before the retention test, and vinburnine was injected 30 min later. For pentylenetetrazol-induced amnesia, pentylenetetrazol was injected 1 hr before the retention test, inducing seizures 30-60 sec later; vinburnine was injected 30 min after pentylenetetrazol. [3] - Behavioral Tests (Rats - Shuttle-box Active Avoidance): Rats were trained in a shuttle-box to avoid a footshock (0.20 mA) signaled by a 3-sec buzzer. A maximum of 30 trials were given. The learning criterion was 5 consecutive conditioned avoidance responses (CARs). The total number of CARs and the number of learners were recorded. [3] - Behavioral Tests (Rats - Passive Avoidance): A similar step-through passive avoidance test as described for mice was used for rats. [3] |
| ADME/Pharmacokinetics |
- General: Vinburnine is a derivative with documented cerebral activity. It is a member of the eburnamine-vincamine group of alkaloids. [2]
- Metabolism: Vinburnine has been shown to stimulate glycolysis in red blood cells. [2] |
| Toxicity/Toxicokinetics |
- General Safety: In the double-blind clinical study with 129 patients (mostly geriatric), no major safety concerns occurred. [2]
- Side Effects: In a double-blind, placebo-controlled study in patients with cerebrovascular disorders, the incidence of gastrointestinal side effects was higher under the higher dose (3 x 60 mg) than under placebo. [2] |
| References | |
| Additional Infomation |
- Background: Vinburnine (l-eburnamonine) is an alkaloid from the Vinca minor plant. It belongs to the eburnamine-vincamine group of compounds, which also includes vincamine, vindeburnol, apovincamine, and vinpocetine. These compounds share modulatory effects on brain circulation and neuronal homeostasis, bearing antihypoxic and neuroprotective potencies. [2]
- Mechanism of Action (General): Vinburnine's effects on learning and memory impairments may be partly related to its influence on central cholinergic neurotransmission, as it reversed scopolamine-induced amnesia. It also improves oxygen supply to the brain by facilitating erythrocyte shape changing, increasing glucose consumption and mitochondrial cytochrome-oxidase activity without lactate production. It is a potent blocker of voltage-gated sodium channels. Vinburnine acts as an allosteric modulator of muscarinic acetylcholine receptors, decelerating antagonist binding. [1][2][3] - Clinical Studies (Vinburnine): In a double-blind study of 129 patients with cerebrovascular deficiencies, vinburnine improved 22 of 25 parameters measuring brain function and was superior to placebo. Another double-blind, placebo-controlled study in patients with cerebrovascular disorders found that a daily dose of 3 x 60 mg vinburnine yielded more therapeutic improvement but also more frequent side effects than a single 60 mg daily dose. A double-blind, placebo-controlled study on 40 subjects (20 normal, 20 with diabetic microangiopathy) showed that vinburnine (45 mg i.v. daily) significantly improved transcutaneous oxygen level, red cell ATP and 2,3-diphosphoglycerate contents, plasma viscosity, and red cell deformability. [2] Eburnamonine is an alkaloid. It has been reported to exist in Rauvolfia serpentina, Aspidosperma quebracho-blanco, and other organisms with relevant data. See also: Eburnamonine (note moved to). |
| Molecular Formula |
C19H22N2O
|
|---|---|
| Molecular Weight |
294.398
|
| Exact Mass |
294.173
|
| Elemental Analysis |
C, 77.52; H, 7.53; N, 9.52; O, 5.43
|
| CAS # |
4880-88-0
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| Related CAS # |
94134-60-8 (phosphate); 4880-88-0
|
| PubChem CID |
71203
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
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| Boiling Point |
441.9±33.0 °C at 760 mmHg
|
| Melting Point |
174-177 °C(lit.)
|
| Flash Point |
221.0±25.4 °C
|
| Vapour Pressure |
0.0±1.1 mmHg at 25°C
|
| Index of Refraction |
1.719
|
| LogP |
3.79
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
1
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| Heavy Atom Count |
22
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| Complexity |
492
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC[C@@]12CCCN3[C@@H]1C4=C(CC3)C5=CC=CC=C5N4C(=O)C2
|
| InChi Key |
WYJAPUKIYAZSEM-MOPGFXCFSA-N
|
| InChi Code |
InChI=1S/C19H22N2O/c1-2-19-9-5-10-20-11-8-14-13-6-3-4-7-15(13)21(16(22)12-19)17(14)18(19)20/h3-4,6-7,18H,2,5,8-12H2,1H3/t18-,19+/m1/s1
|
| Chemical Name |
(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
|
| Synonyms |
CH 846; CH-846; Vinburnine; (-)-Eburnamonine; 4880-88-0; Eburnal; Vinburnina; CH846
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~8.3 mg/mL (~28.3 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (2.82 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.83 mg/mL (2.82 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.83 mg/mL (2.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3967 mL | 16.9837 mL | 33.9674 mL | |
| 5 mM | 0.6793 mL | 3.3967 mL | 6.7935 mL | |
| 10 mM | 0.3397 mL | 1.6984 mL | 3.3967 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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