| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
Propentofylline targets multiple pathways: it antagonizes A1 and A2A adenosine receptors, thereby reducing adenosine-mediated inhibition of synaptic transmission and promoting vasodilation. It also inhibits cyclic nucleotide phosphodiesterases, increasing intracellular cAMP and cGMP levels. This enhances neuronal survival and suppresses inflammatory responses in microglia and astrocytes. Additionally, it reduces glutamate excitotoxicity and oxidative stress. Its pleiotropic action makes it effective in ischemic and neurodegenerative conditions.
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| ln Vitro |
In vitro, propentofylline reduces glutamate-induced neurotoxicity in primary cortical neurons at concentrations of 10-100 µM. It also decreases the production of pro-inflammatory cytokines (TNF-α, IL-1β) from activated microglia. In cell cultures, it increases cAMP levels and promotes neurite outgrowth. It has been shown to protect against beta-amyloid-induced cell death in PC12 cells. Its antioxidant activity is evidenced by reduced ROS generation in astrocytes. These effects are concentration-dependent and correlate with its PDE inhibitory and adenosine antagonist activities.
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| ln Vivo |
In vivo, propentofylline improves cognitive function in aged rats and in models of Alzheimer's disease (e.g., APP/PS1 transgenic mice). It increases cerebral blood flow in ischemic models, reduces infarct volume, and improves neurological deficits following transient middle cerebral artery occlusion. In a dog model of cognitive dysfunction, chronic oral administration (5 mg/kg) enhanced learning and memory. It also exhibits anti-inflammatory effects in spinal cord injury models. Clinical trials in humans have shown modest benefits in dementia, but inconsistent results have limited its regulatory approval.
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| Enzyme Assay |
In cell-free assays, propentofylline's PDE inhibition is measured using purified PDE enzymes and a fluorescent substrate (e.g., cGMP or cAMP) in a reaction buffer, followed by detection of the hydrolyzed product. The IC50 for PDE1 is approximately 20 µM, for PDE4 ~15 µM, and for PDE5 ~30 µM. Adenosine receptor binding is assessed by radioligand displacement using [3H]DPCPX (A1) or [3H]CGS-21680 (A2A) in membrane preparations from rat brain. Ki values are in the low micromolar range. These cell-free assays confirm its multi-target profile and help in structure-activity relationship studies.
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| Cell Assay |
In cellular assays, primary neuronal cultures or microglial cell lines are treated with propentofylline (1-100 µM) for 24-72 hours. Cell viability is measured by MTT or LDH release. For mechanistic studies, cAMP levels are quantified by ELISA. The drug's ability to modulate calcium influx is studied using Fluo-4 AM loading. Inflammatory markers (iNOS, COX-2) are measured by Western blot or qPCR. For neuroprotection, cells are exposed to excitotoxic agents (glutamate, NMDA) with or without the drug, and cell death is assessed. These assays provide evidence for its cytoprotective and anti-inflammatory actions.
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| Animal Protocol |
In animal models of stroke, propentofylline is typically administered intraperitoneally (10-30 mg/kg) or orally (50-100 mg/kg) before or after ischemic insult. Behavioral tests (e.g., rotarod, neurological scores) are performed, and infarct volume is assessed by TTC staining. In cognitive models, it is administered daily for several weeks, and learning and memory are evaluated using the Morris water maze or novel object recognition. Brain tissue is collected for histology (e.g., amyloid plaque load, GFAP staining) and biochemical analyses. In dogs, it is given orally at 5 mg/kg twice daily.
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| ADME/Pharmacokinetics |
Dose-dependent pharmacokinetics in rats show oral bioavailability of about 30-40%, with a half-life of 2-4 hours. It is metabolized in the liver and excreted in urine. It crosses the blood-brain barrier, achieving brain concentrations approximately 30% of plasma levels. In dogs, similar pharmacokinetic parameters are observed. In humans, it has been studied in various formulations, but its development has been hampered by variability. Its metabolism involves demethylation and oxidation. It is not a substrate for major CYP enzymes, but interactions are possible.
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| Toxicity/Toxicokinetics |
Propentofylline is well tolerated in animal studies at therapeutic doses, with no significant organ toxicity in chronic administration (up to 6 months). In dogs, the NOAEL is around 50 mg/kg/day. The most common side effects in animals include mild gastrointestinal disturbance. In clinical trials, adverse effects were mild and transient, including headache, nausea, and flushing. It does not cause severe hepatotoxicity or nephrotoxicity. However, due to its adenosine antagonism, it may increase heart rate; cardiovascular monitoring is advised. Overdose may cause seizures.
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| Additional Infomation |
Propentofylline is an oxopurine drug.
Drug Indications It has been studied for the treatment of Alzheimer's disease.Mechanism of Action Propentofylline is a xanthine derivative and phosphodiesterase inhibitor, and is claimed to have neuroprotective effects. It inhibits the uptake of phosphodiesterase and adenosine. Phosphodiesterase has been shown to be associated with age-related memory impairment and Alzheimer's disease. β-amyloid 1-42 (β42) can induce apoptosis in cultured hippocampal neurons, suggesting its important role in the neurodegenerative changes of Alzheimer's disease. Propentofylline can also activate the cAMP-PKA system, inhibit caspase cascade reactions, and modify Bcl-2 family proteins. Propentofylline inhibited β42-induced apoptosis and further induced the expression of the anti-apoptotic protein Bcl-2. This indicates that the protective effect of Propentofylline against β42-induced neurotoxicity is achieved by enhancing the anti-apoptotic effect of the cAMP-PKA system. Phenylpropionic acid ether (PPE) Propentofylline has been investigated for over three decades and has shown promise in preclinical studies, but its inconsistent clinical efficacy has prevented widespread approval. It is currently approved in some countries (e.g., Japan) for treatment of dementia, but not in the USA or Europe. It is also used in veterinary medicine for canine cognitive dysfunction (brand name Vivitonin). Ongoing research explores its potential in glaucoma, diabetic neuropathy, and retinal diseases due to its vasodilatory effects. It remains a valuable tool for studying the interplay of adenosine and phosphodiesterase pathways in neuroinflammation and neurodegeneration. |
| Molecular Formula |
C15H22N4O3
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|---|---|
| Molecular Weight |
306.36
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| Exact Mass |
306.169
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| CAS # |
55242-55-2
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| PubChem CID |
4938
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
541.4±56.0 °C at 760 mmHg
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| Melting Point |
64-66ºC
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| Flash Point |
281.2±31.8 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.602
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| LogP |
1.38
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
22
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| Complexity |
454
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCN1C=NC2=C1C(=O)N(CCCCC(=O)C)C(=O)N2C
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| InChi Key |
RBQOQRRFDPXAGN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H22N4O3/c1-4-8-18-10-16-13-12(18)14(21)19(15(22)17(13)3)9-6-5-7-11(2)20/h10H,4-9H2,1-3H3
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| Chemical Name |
3-methyl-1-(5-oxohexyl)-7-propylpurine-2,6-dione
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| Synonyms |
HWA285 HWA-285 HWA 285KarsivanHextol Propentophylline
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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) |
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
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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 | 3.2641 mL | 16.3207 mL | 32.6413 mL | |
| 5 mM | 0.6528 mL | 3.2641 mL | 6.5283 mL | |
| 10 mM | 0.3264 mL | 1.6321 mL | 3.2641 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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