| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Based on its structural and pharmacological profile, apovincamine likely acts on multiple cellular targets, similar to the mechanism of vinpocetine. Active compounds in the same family affect calmodulin-dependent phosphodiesterase type I, sodium channels, calcium channels, peripheral benzodiazepine receptors, and glutamate receptors. Among these, phosphodiesterase inhibition is a core mechanism by which these compounds increase cerebral blood flow and exert neuroprotective effects. Additionally, these compounds modulate dopamine release and abnormal neuronal excitability.
|
|---|---|
| ln Vitro |
Apovincamine (cis-Apovincamine; 6.3, 12.5, 25, 50, 100 μM) has anti-melanogenic properties in B16 mouse melanoma cells and dose-dependently decreases cell survival with an IC50 of 49.8 μM [1].
In vitro studies demonstrate that apovincamine exhibits anti-melanogenesis activity in B16 mouse melanoma cells. The compound dose-dependently inhibits cell viability with an IC₅₀ of approximately 49.8 μM. As a member of the eburnamine-vincamine alkaloids, apovincamine may also exert antihypoxic and neuroprotective effects similar to other family members such as vinpocetine. |
| ln Vivo |
The in vivo activity of its structural analogue vinpocetine is well-documented, including increased cerebral blood flow, improved cerebral glucose metabolism, and neuroprotective effects in chronic post-stroke patients. Vinpocetine rapidly penetrates the blood-brain barrier following intravenous administration, with preferential distribution to the thalamus, basal ganglia, and visual cortex. Furthermore, apovincaminic acid, the major active metabolite of vinpocetine, has demonstrated neuroprotective activity in animal models, reducing NMDA-induced lesion size and attenuating behavioral abnormalities.
|
| Enzyme Assay |
For reference, phosphodiesterase inhibition assays for vinpocetine typically use calmodulin-activated phosphodiesterase type I, with [³H]-cAMP or [³H]-cGMP as substrates. Enzyme activity is assessed by detecting the hydrolysis products of the radiolabeled substrates. Assays are typically performed in reaction buffer containing Ca²⁺/calmodulin, followed by pre-incubation with varying concentrations of the compound at 30-37°C, then substrate addition to initiate the reaction. Products are separated and detected using anion exchange resin or scintillation proximity assays.
|
| Cell Assay |
Cell Culture: Culture B16 mouse melanoma cells in DMEM medium containing 10% fetal bovine serum at 37°C in a 5% CO₂ incubator until the logarithmic growth phase.
Drug Treatment: After seeding cells in 96-well plates, treat with varying concentrations of apovincamine (6.3, 12.5, 25, 50, 100 μM) with 3 replicate wells per concentration, and incubate for appropriate duration.
Viability Assay: Measure cell viability using the MTT method to calculate the IC₅₀ value (reported as 49.8 μM).
Melanogenesis Detection: Assess melanin content by measuring absorbance of cell lysates at 405 nm.
Data Analysis: Compare cell viability and melanogenesis levels between treatment and control groups.
|
| Animal Protocol |
Animal Model: Use male Harlan-Wistar rats (300-400 g) and establish a neurotoxicity model by NMDA injection.
Dosing Regimen: Administer apovincaminic acid via intraperitoneal injection at 10 mg/kg twice daily for 4 days.
Behavioral Assessment: Evaluate attention deficits and learning/memory impairment using the spontaneous alternation test and Morris water maze.
Histological Analysis: After euthanasia, collect brain tissue to measure lesion size and assess microglial activation.
Data Analysis: Compare behavioral performance, lesion size, and microglial activation between treatment and control groups.
|
| ADME/Pharmacokinetics |
Apovincamine is a natural alkaloid, and its activity data are primarily based on studies of structural analogues. Regarding pharmacokinetics, the major metabolite of this class of compounds is apovincaminic acid (AVA), which is the active metabolite of vinpocetine. In rats, following oral administration of vinpocetine (apovincaminic acid ethyl ester), absorption is rapid, with a parent drug elimination half-life of < 4.02 hours, and plasma levels of its metabolite apovincaminic acid are ≥ 2.7-fold higher than the parent drug. In humans, following intravenous infusion of vinpocetine (1 mg/kg over 25 minutes), the plasma elimination half-life is 4.7±2.13 hours, with a total clearance of 0.79±0.1 L·h⁻¹·kg⁻¹.
|
| Toxicity/Toxicokinetics |
The oral median lethal dose (LD₅₀) of vinpocetine in rats is approximately 500 mg/kg. In subchronic studies, increased salivation and increased liver and thyroid weights were observed at the highest dose. A report from the National Toxicology Program suggests that vinpocetine may cause harm to pregnant women or the fetus. Following maternal administration, significant transfer of vinpocetine to the fetus was observed (fetal AUC and Cmax ≥ 55% of maternal levels). Patients with low blood pressure, a history of heart problems or stroke, or those taking anticoagulants or antihypertensive medications should exercise caution. Rare adverse events include flushing, rashes, gastrointestinal problems, and decreased white blood cell count.
|
| References | |
| Additional Infomation |
Apovincamine is an alkaloid. It has been reported that Apovincamine is found in Euglena gracilis, and relevant data is available for reference.
|
| Molecular Formula |
C21H24N2O2
|
|---|---|
| Molecular Weight |
336.42746
|
| Exact Mass |
336.184
|
| Elemental Analysis |
C, 74.97; H, 7.19; N, 8.33; O, 9.51
|
| CAS # |
4880-92-6
|
| PubChem CID |
71204
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.3g/cm3
|
| Boiling Point |
405.7ºC at 760mmHg
|
| Melting Point |
160-162℃
|
| Flash Point |
199.1ºC
|
| Index of Refraction |
1.678
|
| LogP |
3.696
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
25
|
| Complexity |
603
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
COC(C1=CC2(CC)CCCN3CCC4C5=CC=CC=C5N1C=4C23)=O
|
| InChi Key |
OZDNDGXASTWERN-CTNGQTDRSA-N
|
| InChi Code |
InChI=1S/C21H24N2O2/c1-3-21-10-6-11-22-12-9-15-14-7-4-5-8-16(14)23(18(15)19(21)22)17(13-21)20(24)25-2/h4-5,7-8,13,19H,3,6,9-12H2,1-2H3/t19-,21+/m1/s1
|
| Chemical Name |
methyl (15S,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18),16-pentaene-17-carboxylate
|
| Synonyms |
Apovincamine; 4880-92-6; cis-Apovincamine; Apovincamina; methyl (15S,19S)-15-ethyl-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18),16-pentaene-17-carboxylate;
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9724 mL | 14.8619 mL | 29.7239 mL | |
| 5 mM | 0.5945 mL | 2.9724 mL | 5.9448 mL | |
| 10 mM | 0.2972 mL | 1.4862 mL | 2.9724 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
