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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.
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 |
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| 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 |
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| 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 |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
IκB kinase (IKK) complex [1] - Phosphodiesterase (PDE)[1] |
| 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]. In murine macrophage RAW264.7 cells and human HeLa cells, Vinpocetine (RGH-4405; AY-27,255) (1-50 μM) dose-dependently inhibited NF-κB activation induced by LPS or TNF-α. At 20 μM, it reduced NF-κB luciferase reporter activity by 65% and suppressed the phosphorylation of IKKα/β (by 58%) and IκBα (by 62%) without affecting total IKKα/β or IκBα protein levels. The drug also downregulated the mRNA and protein expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokines (MCP-1) in LPS-stimulated RAW264.7 cells, with a 55-70% reduction at 30 μM[1] - In human cerebral microvascular endothelial cells (HCMECs), Vinpocetine (RGH-4405; AY-27,255) (5-20 μM) improved endothelial cell viability under hypoxia (1% O₂) conditions. At 15 μM, it increased cell survival rate by 42% and enhanced nitric oxide (NO) production by 50% via upregulating endothelial nitric oxide synthase (eNOS) phosphorylation. Additionally, it reduced hypoxia-induced reactive oxygen species (ROS) generation by 48% at 20 μM[2] |
| 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]. In LPS-induced sepsis mouse model, intraperitoneal administration of Vinpocetine (RGH-4405; AY-27,255) (20 mg/kg, 30 mg/kg, single dose 1 hour after LPS injection) dose-dependently improved survival rate. The 30 mg/kg dose increased 72-hour survival rate from 30% (control) to 75%. It also reduced serum levels of TNF-α, IL-6, and IL-1β by 68%, 72%, and 65% respectively, and inhibited NF-κB activation in liver and lung tissues[1] - In middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia rat model, oral administration of Vinpocetine (RGH-4405; AY-27,255) (10 mg/kg, 20 mg/kg, once daily for 7 days starting 2 hours after ischemia) reduced cerebral infarct volume by 35% (10 mg/kg) and 52% (20 mg/kg). It improved neurological deficit scores by 40% (20 mg/kg) and enhanced cerebral blood flow by 55% in the ischemic penumbra. Histological analysis showed reduced neuronal apoptosis and microglial activation in the infarct area[2] |
| Enzyme Assay |
IKK activity assay: Recombinant IKKα/β complex was incubated with purified IκBα substrate and different concentrations of Vinpocetine (RGH-4405; AY-27,255) (5-50 μM) at 37°C for 1 hour. The reaction mixture was subjected to SDS-PAGE and Western blot using phospho-specific IκBα antibody to detect phosphorylated IκBα. The intensity of the phosphorylated band was quantified to evaluate IKK inhibition[1] - PDE activity assay: Human recombinant PDE1-5 isoforms were incubated with cyclic nucleotide substrate and Vinpocetine (RGH-4405; AY-27,255) (10-100 μM) at 30°C for 30 minutes. The amount of hydrolyzed cyclic nucleotide was measured by radioimmunoassay. No significant inhibition of PDE activity was observed at any tested concentration[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. NF-κB activation assay: RAW264.7 cells or HeLa cells transfected with NF-κB luciferase reporter plasmid were seeded in 96-well plates. Vinpocetine (RGH-4405; AY-27,255) (1-50 μM) was added 1 hour before stimulation with LPS (1 μg/mL) or TNF-α (10 ng/mL). After 6 hours of incubation, cells were lysed, and luciferase activity was measured to assess NF-κB activation[1] - Cytokine detection assay: RAW264.7 cells were seeded in 24-well plates and treated with Vinpocetine (RGH-4405; AY-27,255) (5-30 μM) plus LPS. After 24 hours, cell culture supernatant was collected to measure cytokine levels by ELISA. Total RNA was extracted for qPCR analysis of cytokine mRNA expression[1] - Hypoxic endothelial cell assay: HCMECs were seeded in 96-well plates and exposed to 1% O₂ hypoxia environment. Vinpocetine (RGH-4405; AY-27,255) (5-20 μM) was added at the start of hypoxia. After 24 hours, cell viability was detected by MTT assay. ROS generation was measured using a fluorescent probe, and eNOS phosphorylation was analyzed by Western blot[2] |
| 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. LPS-induced sepsis model: Male C57BL/6 mice (20-25 g) were intraperitoneally injected with LPS (10 mg/kg) to induce sepsis. Vinpocetine (RGH-4405; AY-27,255) was dissolved in DMSO and normal saline (DMSO final concentration ≤5%) and administered intraperitoneally at 20 mg/kg or 30 mg/kg 1 hour after LPS injection. Control mice received equal volume of vehicle. Survival was monitored every 12 hours for 72 hours, and serum and tissue samples were collected at 6 hours post-LPS for cytokine and NF-κB analysis[1] - MCAO cerebral ischemia model: Male Sprague-Dawley rats (250-300 g) were subjected to MCAO surgery to induce focal cerebral ischemia. Vinpocetine (RGH-4405; AY-27,255) was suspended in 0.5% carboxymethylcellulose sodium (CMC-Na) and administered orally at 10 mg/kg or 20 mg/kg 2 hours after ischemia, then once daily for 7 days. Control rats received equal volume of 0.5% CMC-Na. Neurological deficit scores were evaluated daily, and cerebral blood flow was measured by laser Doppler flowmetry. Rats were euthanized on day 7 for infarct volume measurement and histological analysis[2] |
| Toxicity/Toxicokinetics |
In vitro toxicity: Vinpocetine (RGH-4405; AY-27,255) showed low cytotoxicity to RAW264.7, HeLa, and HCMECs, with IC50 values >100 μM[1][2] - In vivo toxicity: In animal experiments, doses up to 40 mg/kg (intraperitoneal) or 30 mg/kg (oral) for 7 days did not cause significant weight loss, abnormal behavior, or changes in liver/kidney function indicators (ALT, AST, BUN, creatinine)[1][2] - Clinical-related side effects: The drug may cause mild adverse reactions such as headache, dizziness, and gastrointestinal discomfort in clinical use[2] |
| 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. Vinpocetine (RGH-4405; AY-27,255) is a synthetic derivative of vincamine, clinically used for the treatment of cerebrovascular diseases such as cerebral ischemia, dementia, and vertigo[2] - Its anti-inflammatory mechanism is IKK-dependent but PDE-independent, inhibiting NF-κB activation to reduce pro-inflammatory cytokine production, which expands its therapeutic potential beyond cerebrovascular diseases[1][3] - The drug exerts neuroprotective effects in cerebral ischemia by improving cerebral blood flow, reducing oxidative stress, inhibiting neuronal apoptosis, and suppressing neuroinflammation[2] - It is recognized as a potent anti-inflammatory agent with broad application prospects in inflammatory diseases, complementing its traditional cerebrovascular therapeutic effects[3] |
Solubility Data
| Solubility (In Vitro) |
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| 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. 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 |