Metamizole sodium's IC50 value for blocking COX-3 in insect cells is 52 μM, while its concentration for blocking COX-1 is 6.6 times greater [2]. The growth of pancreatic cancer cells is markedly inhibited by methimizole (1–500 μM; 48 hours) [3].

Rats treated with 500 mg/kg of metamizole sodium intraperitoneally twice a day for seven days show less development of neuropathic pain symptoms [4].

Cell proliferation assay [3]
Cell Types: Pancreatic cancer cell lines PaTu 8988t and Panc-1
Tested Concentrations: 1 μM, 10 μM, 100 μM, 250 μM, 500 μM
Incubation Duration: 48 hrs (hours)
Experimental Results: PaTu 8988t Dramatically inhibited cell proliferation cells line; 1-250 μM Dramatically inhibits cell proliferation of pancreatic cancer cell line Panc-1.

Animal/Disease Models: Male Wistar rat (270-300 g) with peripheral neuropathic pain [4]
Doses: 500 mg/kg
Route of Administration: intraperitoneal (ip) injection twice (two times) daily for 7 days
Experimental Results: Reduction of pro-nociceptive leukocytes The expression of interleukins (IL-1beta) and chemokines (CCL2, CCL4 and CCL7) in the DRG was measured 7 days after sciatic nerve injury.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
After ingestion by the mother, dipyrone and its metabolites appear in breastmilk in rather large amounts. It is found in the blood and urine of breastfed infants and can cause pharmacological effects in the breastfed infant. One case of cyanotic episodes in a breastfed infant was attributed to dipyrone in breastmilk. The drug and metabolites are eliminated from the breastmilk by 48 hours after a dose.
Dipyrone is not approved for marketing in the United States by the U.S. Food and Drug Administration nor in Canada and many European countries because of its adverse reactions, including agranulocytosis. However, it is widely used in other countries during labor and breastfeeding. The European Medicines Agency recommends that dipyrone not be used in nursing mothers; however, several drug consultation centers in Israel disagree. One manufacturer recommends to withhold breastfeeding for 48 hours after a dose. Safer alternatives are available for analgesia during breastfeeding.
◉ Effects in Breastfed Infants
A 42-day-old breastfed infant had 2 cyanotic episodes within 30 minutes after his mother took 3 doses of dipyrone 500 mg orally, 18, 7 and 2 hours before the first episode. A third episode occurred 24 hours after admission to the hospital. Dipyrone was detected in the mother's breastmilk 24 hours after the last dose and in the infant's serum and urine. No explanation could be found for the cyanotic episodes other than dipyrone and after suspending maternal dipyrone intake, no further episodes occurred in the infant up to age 3 years. The reaction is rated as possibly caused by dipyrone in breastmilk.
In a blinded study, mothers who were at least 3 days postpartum and requesting analgesia for postpartum uterine pain were given either 1 gram of dipyrone or placebo. The infants of mothers who received dipyrone cried fewer times and for shorter durations in the 14 hours after drug administration than the infants of mothers who received placebo. This effect was more apparent in infants who demand fed than in those who fed on a fixed schedule. Although this study appears to demonstrate a pharmacologic effect in the infants from dipyrone in milk, there is no clear explanation for the change in infant behavior.
A multicenter case-control study in Brazil compared 231 children who developed leukemia before 2 years of age with 411 children with various other nonmalignant diseases. Mothers were interviewed to ascertain their analgesic use during pregnancy and lactation. Nursing mothers who took dipyrone during the three months after delivery had a 2-fold risk of having a child with acute lymphocytic leukemia and a 3.87-fold risk in having rearrangement of the MLL gene in infants under one year of age.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. A Jasiecka, et al. Pharmacological characteristics of metamizole. Pol J Vet Sci. 2014;17(1):207-14.
[2]. N V Chandrasekharan, et al. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 2002 Oct 15; 99(21): 13926-13931.
[3]. Manuela Malsy, et al. Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1. BMC Pharmacol Toxicol. 2017 Dec 6;18(1):77.
[4]. Renata Zajaczkowska, et al. Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain. Pharmacol Rep. 2020 Oct;72(5):1310-1322.

Metamizole sodium is an organic sodium salt of antipyrine substituted at C-4 by a methyl(sulfonatomethyl)amino group, commonly used as a powerful analgesic and antipyretic. It has a role as a non-narcotic analgesic, an antirheumatic drug, a peripheral nervous system drug, an antipyretic, a prodrug, a cyclooxygenase 3 inhibitor and an anti-inflammatory agent. It contains a metamizole(1-).
A drug that has analgesic, anti-inflammatory, and antipyretic properties. It is the sodium sulfonate of AMINOPYRINE.

C13H16N3NAO4S

333.3386

333.075

68-89-3

Metamizole sodium hydrate;5907-38-0

522325

Typically exists as solid at room temperature

187ºC

1.504

0

6

4

22

552

0

S(C([H])([H])N(C([H])([H])[H])C1C(N(C2C([H])=C([H])C([H])=C([H])C=2[H])N(C([H])([H])[H])C=1C([H])([H])[H])=O)(=O)(=O)[O-].[Na+]

DJGAAPFSPWAYTJ-UHFFFAOYSA-M

InChI=1S/C13H17N3O4S.Na/c1-10-12(14(2)9-21(18,19)20)13(17)16(15(10)3)11-7-5-4-6-8-11;/h4-8H,9H2,1-3H3,(H,18,19,20);/q;+1/p-1

sodium;[(1,5-dimethyl-3-oxo-2-phenylpyrazol-4-yl)-methylamino]methanesulfonate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)