| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
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| 50mg |
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| 100mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
The primary target of velnacrine is acetylcholinesterase (AChE), acting via inhibition of this enzyme. Additionally, in vitro neuromuscular studies have shown that velnacrine exhibits nonselective blocking actions on potassium channels at motor nerve terminals at high concentrations, though this effect is only observed at elevated concentrations. Velnacrine also inhibits butyrylcholinesterase (BuChE) activity and has been used as a positive control in AChE inhibitor screening studies.
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| ln Vitro |
In vitro studies demonstrate that velnacrine acts primarily as an anticholinesterase agent. In isolated chick biventer cervicis preparations, velnacrine augments responses to nerve stimulation and increases responses to exogenously applied acetylcholine, indicating its classical anticholinesterase activity. In mouse diaphragm preparations, velnacrine reverses twitch block induced by tubocurarine or low calcium solutions. Additionally, velnacrine’s inhibition of AChE has been used to validate the activity of metabolites from marine fungi, serving as a positive control with its IC₅₀ value compared to other known inhibitors.
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| ln Vivo |
Clinical studies demonstrate that velnacrine can slow cognitive decline in patients with Alzheimer's disease. In a 6-week US dose-finding trial involving 425 Alzheimer's patients, about one-third showed modest clinical improvement with velnacrine at doses up to 225 mg/day. In a 24-week double-blind, placebo-controlled Phase III trial, the 12-week interim analysis showed that the 150 mg/day and 225 mg/day dose groups were superior to placebo; notably, at the 24-week assessment, caregiver time was significantly shorter for velnacrine recipients compared to placebo recipients.
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| Enzyme Assay |
Enzyme Source Preparation: Use electric eel-derived or human erythrocyte-derived acetylcholinesterase.
Substrate Preparation: Use a modified Ellman colorimetric method with acetylthiocholine iodide as substrate, prepared with DTNB in phosphate buffer (pH 7.4).
Inhibitor Incubation: Pre-incubate varying concentrations of velnacrine with the enzyme in buffer at 37°C.
Reaction Initiation and Detection: Initiate the reaction by adding substrate and measure absorbance changes at 412 nm.
Data Analysis: Calculate IC₅₀ values; velnacrine is often used as a positive control in such studies.
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| Cell Assay |
Cell Culture: Use neuronal cell lines (e.g., PC12 cells) or primary neurons for related studies.
Drug Treatment: Add varying concentrations of velnacrine (e.g., 1-100 µM) and incubate for 24-72 hours.
Viability Assay: Measure cell viability using MTT or CCK-8 assays.
AChE Activity Assay: Lyse cells and measure intracellular AChE activity using the Ellman method.
Data Analysis: Calculate cell viability and enzyme inhibition rates at each concentration.
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| Animal Protocol |
Animal Selection: Use mice for behavioral and pharmacodynamic studies.
Dosing Regimen: Velnacrine can be administered via oral gavage or intraperitoneal injection.
Model Induction: Use scopolamine to induce memory impairment in mice.
Behavioral Assessment: Evaluate learning and memory capacity using the Morris water maze or passive avoidance test.
Metabolism Studies: Administer [¹⁴C]-labeled velnacrine, collect plasma, urine, and feces, and detect radioactivity by liquid scintillation counting.
Data Analysis: Compare cognitive behavior and pharmacokinetic parameters between treatment and control groups.
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| ADME/Pharmacokinetics |
Metabolism/Metabolites
N4-hydroxylamine is a known human metabolite of tacrine. Velnacrine is rapidly absorbed after oral administration. Multiple-dose pharmacokinetic studies in healthy elderly male subjects demonstrated dose-related increases in Cmax, AUC, and amount of drug excreted in urine. The tmax and t½ were not affected by dosage nor by multiple dosing. Steady-state levels were reached between days 2 and 3 with no evidence of further accumulation thereafter. Approximately 11-30% of the administered dose was excreted unchanged in the urine over the course of the study. |
| Toxicity/Toxicokinetics |
The primary target organ of velnacrine toxicity is the liver. In a US dose-finding trial, 27% of participants discontinued treatment due to elevated plasma hepatic enzyme levels. Other adverse events leading to withdrawal included rash, nausea, diarrhea, headache, and dizziness/fainting. Neutropenia was also reported in a few patients. Gastrointestinal side effects (primarily diarrhea) were also common, with approximately nine subjects reporting one or two episodes during a 29-day trial, but none required treatment or were discontinued from the study. In a study of healthy elderly men, no evidence of hepatotoxicity was observed with 100 mg tid for 28 days.
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| References | |
| Additional Infomation |
9-Amino-1,2,3,4-Tetrahydroacridine-1-ol is a member of the acridine class of compounds.
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| Molecular Formula |
C13H14N2O
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|---|---|
| Molecular Weight |
214.26306
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| Exact Mass |
214.11
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| Elemental Analysis |
C, 72.87; H, 6.59; N, 13.07; O, 7.47
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| CAS # |
124027-47-0
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| Related CAS # |
118909-22-1
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| PubChem CID |
3655
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| Appearance |
White to off-white solid at room temperature
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| Boiling Point |
450.3 °C at 760 mmHg
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| Melting Point |
245℃
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| LogP |
1.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
16
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| Complexity |
258
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C(=N)C3=C(CCCC3O)N2
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| InChi Key |
HLVVITIHAZBPKB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H14N2O/c14-13-8-4-1-2-5-9(8)15-10-6-3-7-11(16)12(10)13/h1-2,4-5,11,16H,3,6-7H2,(H2,14,15)
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| Chemical Name |
9-amino-1,2,3,4-tetrahydroacridin-1-ol
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 2.9 mg/mL (13.4 mM)
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|---|---|
| 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 | 4.6672 mL | 23.3361 mL | 46.6723 mL | |
| 5 mM | 0.9334 mL | 4.6672 mL | 9.3345 mL | |
| 10 mM | 0.4667 mL | 2.3336 mL | 4.6672 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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