| Size | Price | Stock | Qty |
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| 500mg |
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| 5g |
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| Other Sizes |
| Targets |
Cyclic GMP phosphodiesterase (PDE) from guinea-pig trachealis muscle. The IC50 value for inhibition of cyclic GMP PDE by 3-Methylxanthine is 920 μmol/L. [1]
Central nervous system (CNS), leading to clonic convulsions. [2] |
|---|---|
| ln Vitro |
3-Methylxanthine relaxed isolated guinea-pig trachealis preparations with spontaneous tone. The -log EC50 value for this relaxation was 3.85 ± 0.05 mol/L. This relaxant potency was significantly less (P<0.01) than that of the corresponding 1-methyl-3-alkylxanthine (theophylline, -log EC50 4.55 ± 0.13). The potency was increased by increasing the length of the alkyl chain at position 3 and by methylation at position 1. [1]
There was a strong positive correlation (r = 0.9319, P<0.001) between the concentration of 3-Methylxanthine which inhibited cyclic GMP PDE by 50% (IC50) and its EC50 value for trachealis muscle relaxation. [1] |
| Enzyme Assay |
Cyclic GMP phosphodiesterase (PDE) was purified from the membranous portion of guinea-pig tracheae. The tissue was homogenized in Tris-HCl buffer and centrifuged. The supernatant was salted out with ammonium sulfate and centrifuged again. The precipitate was dialyzed and applied to a DEAE-cellulose column. The column was eluted with a linear concentration gradient of NaCl. The resulting cyclic GMP PDE (Peak 1) was used for inhibition studies. PDE activity was measured by incubating the enzyme with [³H]-cyclic GMP, MgCl₂, and various concentrations of 3-Methylxanthine in Tris-HCl buffer (pH 8.0) for 15 minutes at 30°C. The reaction was stopped by boiling, followed by addition of snake venom to convert the nucleotide product to its nucleoside. The mixture was then passed through a cation-exchange resin column, and the eluted [³H]-guanosine was quantified by liquid scintillation counting. The IC50 value (920 μmol/L) was determined from the resulting concentration-response curves. [1]
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| Cell Assay |
Guinea-pig trachealis muscle relaxation: Tracheal rings from male Hartley guinea-pigs were opened and ligated. The preparation was mounted in a 1 mL organ bath and perfused at 1.5 mL/min with Krebs' solution at 37°C. An initial tension of about 0.5 g was applied. After spontaneous tone developed and stabilized, the preparation was perfused for 20 minutes with various concentrations of 3-Methylxanthine. Relaxation was measured using an isometric transducer and recorded. The relaxation caused by a Ca²⁺-free medium containing EGTA was defined as 100% relaxation, and the relaxation caused by 3-Methylxanthine was calculated relative to this standard. The -log EC50 value was determined from log concentration-relaxation curves derived from experiments on specimens from six guinea-pigs. [1]
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| Animal Protocol |
For intracerebral administration: Male ddY mice (5 weeks, 20-30 g) were given 10 μl of a 3-Methylxanthine solution directly into the right lateral ventricle (3 mm anterior, 2 mm left, and 4 mm depth relative to the lambdoid suture). The mice were then observed for 20 minutes for the occurrence of clonic convulsion. The drug was dissolved in a small amount of 1 M NaOH, pH adjusted to 7-11 with 1 M HCl, and diluted with water, maintaining osmotic pressure between 150-560 mOsm and chloride concentration between 150-200 meq/l. [2]
For intravenous infusion: 3-Methylxanthine solution was infused into the tail vein of male ddY mice at a constant rate of 24.1 μl/min until the onset of clonic convulsion. At the onset of convulsion, the infusion was stopped, and the mouse was decapitated to collect blood and brain samples. If no convulsion was observed, the infusion was stopped at 60 minutes. [2] |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
3-Methylxanthine is a known metabolite of theophylline and theobromine in the human body. Following intravenous infusion of 3-Methylxanthine to mice until the onset of convulsion, the mean total dose infused was 7.48 ± 0.67 mmol/kg, the mean plasma concentration (Cp) at the end of infusion was 5.21 ± 0.63 mM, and the mean brain concentration (Cb) was 0.81 ± 0.18 μmol/g. The brain-to-plasma concentration ratio (Cb/Cp) was 0.16 ± 0.05 ml/g. [2] 3-Methylxanthine was detected in the plasma and brain of mice after intravenous infusion of theophylline. The brain concentration of 3-MX at the onset of theophylline-induced convulsion was 0.024 ± 0.008 μmol/g. [2] |
| Toxicity/Toxicokinetics |
3-Methylxanthine induced clonic convulsion in a dose-dependent manner after intracerebral administration to mice. The ED50 value for clonic convulsion was 1107 ± 104 nmol/body. The slope factor (γ) for the dose-response curve was 1.41 ± 2.19. [2]
Clonic convulsion was induced by intravenous infusion of 3-Methylxanthine to mice. The onset time was 24.5 ± 2.4 minutes, and the total dose at onset was 7.48 ± 0.67 mmol/kg. [2] There was no significant difference between the threshold brain concentration of 3-Methylxanthine and theophylline for inducing convulsion. [2] |
| References | |
| Additional Infomation |
3-Methyl-9H-xanthine is a tautomer of 3-methylxanthine, in which the imidazole proton is located at position 9. It is a metabolite and also a tautomer of 3-methyl-7H-xanthine. 3-Methylxanthine has been reported in Arabidopsis thaliana, honeybee, and Wedelia triloba, and relevant data are available for reference.
In the context of asthma treatment, the mechanism of action of xanthine derivatives like theophylline was not yet clarified. While cyclic GMP was initially considered to exert bronchoconstriction, later findings suggested it is a second messenger for airway smooth muscle relaxation, similar to cyclic AMP. This study aimed to clarify if cyclic GMP PDE inhibition is involved in the tracheal relaxant effect of xanthines. [1] It is known that about 90% of a theophylline dose is excreted in urine as metabolites, including 3-Methylxanthine. The pharmacological efficacy of these metabolites is relatively weak compared to the parent compound. However, this study on neurotoxic convulsions investigated whether theophylline metabolites have intrinsic neurotoxic potency, especially in disease states like renal failure where blood-brain barrier permeability might be altered. [2] 3-Methylxanthine is detected in plasma and urine of humans administered theophylline. Its accumulation due to renal insufficiency may induce neurotoxicity even if the theophylline level is in the sub-therapeutic range. [2] |
| Molecular Formula |
C6H6N4O2
|
|---|---|
| Molecular Weight |
166.1374
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| Exact Mass |
166.049
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| CAS # |
1076-22-8
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| Related CAS # |
3-Methylxanthine-13C4,15N3;1173018-93-3
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| PubChem CID |
70639
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| Appearance |
Solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
322.4ºC at 760 mmHg
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| Melting Point |
>300 °C(lit.)
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| Flash Point |
148.8ºC
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| Vapour Pressure |
2.23E-05mmHg at 25°C
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| Index of Refraction |
1.627
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| LogP |
-0.79
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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 |
12
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| Complexity |
242
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GMSNIKWWOQHZGF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H6N4O2/c1-10-4-3(7-2-8-4)5(11)9-6(10)12/h2H,1H3,(H,7,8)(H,9,11,12)
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| Chemical Name |
3-methyl-7H-purine-2,6-dione
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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) |
1M NaOH : 50 mg/mL (~300.95 mM)
DMSO : ~2.61 mg/mL (~15.71 mM) Ethanol :< 1 mg/mL DMF :< 1 mg/mL H2O : < 0.1 mg/mL |
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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 | 6.0190 mL | 30.0951 mL | 60.1902 mL | |
| 5 mM | 1.2038 mL | 6.0190 mL | 12.0380 mL | |
| 10 mM | 0.6019 mL | 3.0095 mL | 6.0190 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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