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Vinpocetine (RGH-4405; AY-27,255)

Alias: RGH-4405; TCV 3B,apovincaminic acid ethyl ester, ethyl apovincaminate, AY 27,255, RGH 4405, TCV-3B,AY-27,255,RGH4405, TCV3B, Cavinton, Intelectol
Cat No.:V1662 Purity: ≥98%
Vinpocetine (formerly RGH-4405; AY-27,255;AY27,255,RGH4405, TCV-3B, Cavinton, Intelectol; Ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine which is a natural product extracted from either the seeds of Voacanga africana or the leaves of Vinca minor as well as the lesser periwinkle plant.
Vinpocetine (RGH-4405; AY-27,255)
Vinpocetine (RGH-4405; AY-27,255) Chemical Structure CAS No.: 42971-09-5
Product category: Sodium Channel
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
250mg
500mg
1g
Other Sizes

Other Forms of Vinpocetine (RGH-4405; AY-27,255):

  • Vinpocetine-d5 (vinpocetine d5)
Official Supplier of:
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Vinpocetine (formerly RGH-4405; AY-27,255; AY27,255, RGH4405, TCV-3B, Cavinton, Intelectol; Ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine which is a natural product extracted from either the seeds of Voacanga africana or the leaves of Vinca minor as well as the lesser periwinkle plant. It is a selective voltage-sensitive sodium channel blocker for the treatment of stroke, vascular dementia and Alzheimer's disease. Vinpocetine has been reported to have a selective and noncompetitive inhibition of Ca2+ PDE and thus regulate cyclic GMP levels in smooth muscle. In addition, vinpocetine has been revealed to inhibit the activities of three resolvable PDE in the cytosol of rat aorta with Ki values of 14±2μM, >1000μM and >1000μM for Ca2+ PDE(+)CaM, cGMP PDE and cAMP PDE, respectively.

Biological Activity I Assay Protocols (From Reference)
ln Vitro
Vinpocetine (5-50 μM; 7 hours; VSMC, HUVEC, A549 cells, and RAW264.7 cells) potently suppresses TNF-α-induced NF-κB-dependent transcriptional activity in a dose-dependent manner, with an approximate IC50 value of 25 μM. Vinpocetine has no substantial effect on cell viability [1]. Vinpocetine (50 μM; 7 hours; VSMC, HUVEC, A549 cells, and RAW264.7 cells) substantially suppresses TNF-α-induced TNF-α, IL-1β, IL-8, MCP-1, VCAM- in different cell types 1. Upregulation of ICAM-1 and MIP-2 transcripts [1].
ln Vivo
In mouse models of α- or LPS-induced lung inflammation, vinpocetine (2.5–10 mg/kg; i.p.; C57BL/6 mice) effectively reduces TNF–Interstitial infiltration of polymorphonuclear leukocytes and inhibits the upregulation of pro-inflammatory mediators, such as TNF-α, IL-1β, and MIP-2 [1].
Cell Assay
RT-PCR[1]
Cell Types: VSMCs, HUVECs, A549 cells and RAW264.7 cells
Tested Concentrations: 50 μM
Incubation Duration: 7 hrs (hours)
Experimental Results: Inhibited TNF-α-induced up-regulation of TNF-α, IL-1β, IL -8, MCP-1, VCAM-1, ICAM-1and MIP-2 transcripts in several cell types.
Animal Protocol
Animal/Disease Models: C57BL/6 mice (8 weeks of age)[1]
Doses: 2.5 mg/kg, 5 mg/kg, and 10 mg/kg
Route of Administration: intraperitoneal (ip)injection
Experimental Results: Inhibited TNF-α- or LPS-induced up- Regulation of proinflammatory mediators, including TNF-α, IL-1β, and MIP-2, and diminished interstitial infiltration of polymorphonuclear leukocytes in a mouse model of TNF-α- or LPS-induced lung inflammation.
References

[1]. Vinpocetine inhibits NF-κB-dependent inflammation via an IKK-dependent but PDE-independent mechanism PNAS May 25, 2010 vol. 107 no. 21 9795-9800.

[2]. Role of vinpocetine in cerebrovascular diseases. Pharmacol Rep. 2011;63(3):618-28.

[3]. Alexandre E. Medina Vinpocetine as a potent antiinflammatory agent PNAS June 1, 2010, Vol. 107, No. 22 9921-9922.

Additional Infomation
Vinpocetine is an alkaloid. It has a role as a geroprotector.
Vinpocetine has been investigated for the treatment of Epilepsy.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C22H26N2O2
Molecular Weight
350.45
Exact Mass
350.199
CAS #
42971-09-5
Related CAS #
Vinpocetine-d5;2734920-39-7
PubChem CID
443955
Appearance
White to off-white solid powder
Density
1.3±0.1 g/cm3
Boiling Point
419.5±45.0 °C at 760 mmHg
Melting Point
147-153ºC dec
Flash Point
207.5±28.7 °C
Vapour Pressure
0.0±1.0 mmHg at 25°C
Index of Refraction
1.666
LogP
5.14
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
3
Rotatable Bond Count
4
Heavy Atom Count
26
Complexity
617
Defined Atom Stereocenter Count
2
SMILES
CC[C@@]12CCCN3[C@@H]1C4=C(CC3)C5=CC=CC=C5N4C(=C2)C(=O)OCC
InChi Key
DDNCQMVWWZOMLN-IRLDBZIGSA-N
InChi Code
InChI=1S/C22H26N2O2/c1-3-22-11-7-12-23-13-10-16-15-8-5-6-9-17(15)24(19(16)20(22)23)18(14-22)21(25)26-4-2/h5-6,8-9,14,20H,3-4,7,10-13H2,1-2H3/t20-,22+/m1/s1
Chemical Name
ethyl (41S,13aS)-13a-ethyl-2,3,41,5,6,13a-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate
Synonyms
RGH-4405; TCV 3B,apovincaminic acid ethyl ester, ethyl apovincaminate, AY 27,255, RGH 4405, TCV-3B,AY-27,255,RGH4405, TCV3B, Cavinton, Intelectol
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 Data
Solubility (In Vitro)
DMSO:3 mg/mL (8.6 mM)
Water:<1 mg/mL
Ethanol:<1 mg/mL
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 0.62 mg/mL (1.77 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 6.2 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 0.62 mg/mL (1.77 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 6.2 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.

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Solubility in Formulation 3: ≥ 0.62 mg/mL (1.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 6.2 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.8535 mL 14.2674 mL 28.5347 mL
5 mM 0.5707 mL 2.8535 mL 5.7069 mL
10 mM 0.2853 mL 1.4267 mL 2.8535 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.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02011971 SUSPENDED Drug: Vinpocetine Epilepsy Stanford University 2012-02 Phase 1
Phase 2
NCT06441591 RECRUITING Drug: Vinpocetine
Drug: Standard Therapy
Other: Placebo
Diabetic Kidney Disease
Diabetic Nephropathies
Ain Shams University 2024-06-01 Phase 2
Phase 3
NCT02878772 COMPLETED Drug: vinpocetine
Drug: Aspirin
Vinpocetine
Immunoregulation
Inflammation
Stroke
Tianjin Medical University
General Hospital
2014-05 Phase 2
Phase 3
NCT01400035 COMPLETED Cerebral Infarction Shanghai Rxmidas
Pharmaceuticals Co. Ltd.
2010-05
NCT02857829 COMPLETED Dietary Supplement: CAF+
Dietary Supplement: Caffeine-alone
Other: Placebo
Biomedical Enhancement Nootrobox, Inc. 2017-03-01 Not Applicable
Biological Data
  • Vinpocetine (Vinp) inhibits monocyte adhesion of HUVECs and chemotactic activity of VSMCs. (A) Microscopic images showing U937 monocytes adhering to HUVECs as assessed by in vitro adhesion assay. HUVECs were pretreated with vehicle DMSO (0.5% final concentration) or 50 μM Vinp for 60 min before treatment with TNF-α (10 ng/mL) or vehicle for 6 h in the continued presence or absence of Vinp. U937 monocyte adhesion to TNF-α- or vehicle–stimulated HUVECs was analyzed. Con, control. (B) Quantitative monocyte adhesion to HUVECs. (C) Monocyte chemotaxis to VSMCs measured by transwell migration. Rat aortic VSMCs were treated with or without TNF-α (10 ng/mL) for 9 h in the presence or absence of various doses of Vinp (5–50 μM). VSMC-conditional medium was collected and used for monocyte chemotaxis assays in Boyden chambers. Data represent the mean ± SD of at least three independent experiments, and each experiment was performed in triplicate. P < 0.05 vs. control; #P < 0.05 vs. TNF-α alone. Vinpocetine inhibits NF-κB–dependent inflammation via an IKK-dependent but PDE-independent mechanism
  • Vinpocetine (Vinp) inhibits lung inflammatory response in vivo. (A) Vinp administered i.p. (at 2.5, 5, and 10 mg/kg of body weight) significantly inhibited induction of TNF-α, IL-1β, and MIP-2 mRNA in the lungs of mice by intratracheal administration of LPS (2 μg per mouse). Data represent the mean ± SD of at least three independent experiments. *P < 0.05 vs. untreated group; #P < 0.05 vs. LPS alone. (B) Histological analysis (H&E stain) showing that Vinp (10 mg/kg of body weight) inhibited PMN infiltration in BAL fluids from the lungs of mice treated with LPS. Arrows point to PMN. Con, control. (C) Histological analysis showing that Vinp (10 mg/kg of body weight) inhibited leukocyte infiltration in peribronchial and interstitial areas of the lung (H&E stain, magnification ×200). Vinpocetine inhibits NF-κB–dependent inflammation via an IKK-dependent but PDE-independent mechanism
  • Vinpocetine (Vinp) inhibits TNF-α–induced NF-κB activation by targeting IKK. (A) Effects of Vinp on TNF-α–induced IκBα phosphorylation and degradation. Rat aortic VSMCs were treated with TNF-α (10 ng/mL) for different time periods (0–30 min) as indicated, in the presence or absence of 50 μM Vinp. Western blotting analysis was carried out to evaluate the levels of phosphorylated IκBα, total IκBα, and β-actin. (B) Vinp inhibits TNF-α–induced IKK kinase activity in rat aortic VSMCs. VSMCs were treated with TNF-α (10 ng/mL) for 10 min in the presence of Vinp (50 μM) or vehicle. IKK kinase activity was analyzed by an immune complex kinase assay. Effects of Vinp on NF-κB activation induced by expressing CA-MEKK1 (C), CA-IKKα (D), CA-IKKβ (E), or WT p65 (F) in VSMCs are shown. Data represent the mean ± SD of at least three independent experiments. *P < 0.05 vs. vector control group; #P < 0.05 vs. either CA-MEKK1, CA-IKKα, CA-IKKβ, or WT p65 alone. (G) Effects of Vinp on LPS-induced IκBα phosphorylation and degradation in mouse lungs in vivo. The lung tissues of mice treated with or without Vinp and LPS were subjected to Western blotting analyses for the levels of phospho-IκBα and total IκBα. The relative phospho-IκBα (H) and total IκBα (I) levels were quantified by densitometry and normalized to β-actin. Data represent the mean ± SD of at least three animals. *P < 0.05 vs. vehicle control group; #P < 0.05 vs. LPS-alone group. Vinpocetine inhibits NF-κB–dependent inflammation via an IKK-dependent but PDE-independent mechanism
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