| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Cyclooxygenase (COX-1 and COX-2); inhibits prostaglandin E2 (PGE2) production, serving as the primary mediator of the analgesic and antipyretic effects of metamizole.
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| ln Vitro |
In an oxygenated environment and at ambient temperature, the prodrug methimizole spontaneously and non-enzymatically transforms into 4-methylaminoantipyrine. In order to produce 4-formamidoantipyrine, which is then transformed into 4-aminoantipyrine, the N-methyl side chain of 4-methylaminoantipyrine is oxidized. The most significant pyrazolone derivative in terms of pharmacology is 4-methylaminoantipyrine, which is part of the group of compounds known as metamizole when present in an aqueous solution and with oxygen [2].
4-Methylaminoantipyrine inhibits production of prostaglandin E2 (PGE2) with an IC50 in the micromolar range. At 0.1 mM, it significantly reduces PGE2 production in cell-based assays. The compound exhibits analgesic and antipyretic activity, though its anti-inflammatory effects are relatively weak compared to other NSAIDs. |
| ln Vivo |
This study looked at the pharmacokinetics of 4-methylaminoantipyrine, the drug's active metabolite, following a single intramuscular injection of metamizole in male piglets. Metamizole (100 mg/kg) was given intramuscularly into eight healthy male piglets. 4- Quantitative measurements of methylaminoantipyrine plasma concentrations can be made in 0.25 to 48 hours. The 4-methylaminoantipyrine mean maximum concentration was 47.59 mg/mL. 4-methylaminoantipyrine has an average half-life of 8.57 hours [1].
In vivo, 4-methylamino antipyrine mediates the analgesic and antipyretic effects of metamizole. Following oral administration of metamizole, the metabolite is formed rapidly and contributes to the therapeutic effects. It acts centrally to reduce fever and peripherally to alleviate pain through COX inhibition. |
| Enzyme Assay |
COX inhibition assay: Purified COX-1 or COX-2 enzyme (10 nM) is incubated with arachidonic acid (10 uM) and 4-methylamino antipyrine (0.1-1000 uM) in 100 mM Tris-HCl pH 8.0, 5 mM EDTA, 2 mM phenol for 5 minutes at 37degC. The reaction is stopped with 2N HCl, and PGE2 production is measured by ELISA or radioimmunoassay. IC50 values are calculated from dose-response curves.
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| Cell Assay |
PGE2 production assay: RAW 264.7 macrophages or human whole blood are stimulated with LPS (1 ug/mL) and treated with 4-methylamino antipyrine (0.1-1000 uM) for 4-24 hours. Supernatants are collected, and PGE2 levels are quantified by competitive ELISA. Inhibition of PGE2 production is calculated relative to vehicle controls, and IC50 is determined.
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| Animal Protocol |
Rat model of fever: Male Sprague-Dawley rats are injected with yeast (10 mL/kg, s.c.) to induce fever. After fever is established (4 hours), rats are administered 4-methylamino antipyrine (10-100 mg/kg, p.o. or i.p.) or vehicle. Rectal temperatures are measured every 30 minutes for 4 hours. Antipyretic effect is calculated as the reduction in area under the temperature-time curve.
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| ADME/Pharmacokinetics |
Human PK following metamizole administration: 4-Methylaminoantipyrine is the major active metabolite with a Cmax of ~5-10 ug/mL achieved at 1-2 hours after oral metamizole. Elimination half-life is approximately 2-3 hours. The compound is extensively metabolized to other metabolites and excreted in urine. Protein binding is moderate (~50%).
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| Toxicity/Toxicokinetics |
Metamizole and its metabolite 4-methylaminoantipyrine have a well-established safety profile. Common adverse effects include gastrointestinal disturbances, allergic reactions (rash, urticaria), and rare but serious agranulocytosis. The metabolite itself is not associated with unique toxicity beyond that of the parent drug.
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| References |
[1]. Burmańczuk A, et al. Pharmacokinetic investigations of the marker active metabolites 4-methylamino-antipyrine and 4-amino-antipyrine after intramuscular injection of metamizole in healthy piglets. J Vet Pharmacol Ther. 2016 Dec;39(6):616-620.
[2]. Campos C1, et al. Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol. 1999 Aug 13;378(3):339-47. [3]. Ariza A, et al. Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole. Sci Rep. 2016 Mar 31;6:23845. |
| Additional Infomation |
4-Methylamino antipyrine HCl is a research standard, not a drug. It is the major active metabolite of metamizole, a pyrazolone NSAID used in some countries as an analgesic and antipyretic. The compound is used as a reference standard in pharmacokinetic studies and drug metabolism research.
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| Molecular Formula |
C₁₂H₁₆CLN₃O
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|---|---|
| Molecular Weight |
253.73
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| Exact Mass |
253.098
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| CAS # |
856307-27-2
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| Related CAS # |
4-Methylamino antipyrine;519-98-2;4-Methylamino antipyrine-d3 hydrochloride
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| PubChem CID |
54759014
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.401
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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 |
2
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| Heavy Atom Count |
17
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| Complexity |
318
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C1N(C2C=CC=CC=2)N(C)C(C)=C1NC
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| InChi Key |
NNONRTWOIVTAHL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H15N3O.ClH/c1-9-11(13-2)12(16)15(14(9)3)10-7-5-4-6-8-10;/h4-8,13H,1-3H3;1H
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| Chemical Name |
1,5-dimethyl-4-(methylamino)-2-phenylpyrazol-3-one;hydrochloride
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| Synonyms |
4Methylamino antipyrine HCl; 4 Methylamino antipyrine HCl
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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 | 3.9412 mL | 19.7060 mL | 39.4120 mL | |
| 5 mM | 0.7882 mL | 3.9412 mL | 7.8824 mL | |
| 10 mM | 0.3941 mL | 1.9706 mL | 3.9412 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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