Metamizole sodium hydrate (1 and 10 μM, 24 h) suppresses osteoblast development, which lowers the osteoblasts' capacity to create new extracellular matrix that mineralizes bone [2]. In the pancreatic cancer cell lines PaTu 8988 t and Panc-1, metamizole sodium hydrate (1-500 μM, 48 h) can increase cell death and limit cell growth [3].

Rats treated with 500 mg/kg of metamizole sodium hydrate intraperitoneally twice a day for seven days will show less signs of developing neuropathic pain [4]. In rats, oxidative stress brought on by incision and carrageenan can be successfully reduced by oral administration of metamizole sodium hydrate (250 or 500 mg/kg) [5].

Cell Proliferation Assay[3]
Cell Types: PaTu 8988 t, Panc-1
Tested Concentrations: 1, 10, 100, 250, 500 μM
Incubation Duration: 48 h
Experimental Results: Inhibited proliferation in the PaTu 8988 t cell line with 1–500 μM and with concentrations of 1 μM, 10 μM, 100 μM, and 250 μM in the Panc-1 cell line. Increased the apoptosis rate after 9 h.

Animal/Disease Models: Neuropathic pain rat model [4]
Doses: 500 mg/kg
Route of Administration: intraperitoneally preemptively at 16 and 1 h before Chronic constriction injury (CCI) and then twice a day for 7 days.
Experimental Results: diminished the expression of pronociceptive interleukins ( IL-1beta, IL-6, and IL-18) and chemokines (CCL2, CCL4, and CCL7).

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Animal/Disease Models: Pain model in rats [5]
Doses: 250 or 500 mg/kg
Route of Administration: po
Experimental Results: diminished the COX -2 gene expression at 500 mg/kg and increased the MPO gene expression. decreased MDA levels in the carrageenan paw test and increased tGSH levels.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
After a mother takes metamizole, metamizole and its metabolites appear in large quantities in breast milk. Metamizole can also be detected in the blood and urine of breastfed infants and may have pharmacological effects on them. There has been one case of cyanosis in a breastfed infant, which was thought to be caused by metamizole in breast milk. The drug and its metabolites are cleared from breast milk within 48 hours after administration.
Due to adverse reactions including agranulocytosis, the U.S. Food and Drug Administration (FDA) has not approved metamizole for marketing in the United States, Canada, and many European countries. However, in other countries, metamizole is widely used during childbirth and lactation. The European Medicines Agency recommends against the use of metamizole by breastfeeding women; however, several drug advisory centers in Israel disagree. One manufacturer recommends discontinuing breastfeeding within 48 hours of administration. There are safer alternatives for pain relief during lactation.
◉ Effects on Breastfed Infants
A 42-day-old breastfed infant experienced two episodes of cyanosis within 30 minutes of his mother taking three doses of 500 mg metamizole, administered 18 hours, 7 hours, and 2 hours before the first episode. The third episode occurred 24 hours after admission. Metamizole was detected in the mother's breast milk and in the infant's serum and urine 24 hours after the last dose. No other cause of the cyanosis was found besides metamizole. After the mother discontinued metamizole, the infant did not experience any further cyanosis episodes until age 3. This reaction is thought to be possibly caused by metamizole in breast milk.
In a double-blind study, mothers at least 3 days postpartum who requested analgesia due to postpartum uterine pain were randomly assigned to receive either 1 gram of metamizole or a placebo. Infants born to mothers receiving the placebo experienced fewer and shorter crying episodes within 14 hours of administration. This effect was more pronounced in infants fed on demand than in those fed on a schedule. While this study appears to suggest that metamizole in breast milk has a pharmacological effect on infants, there is currently no clear explanation for the changes in infant behavior. A multicenter case-control study in Brazil compared 231 children under 2 years of age with leukemia and 411 children with various other non-malignant diseases. Researchers interviewed mothers to determine their use of analgesics during pregnancy and lactation. Breastfeeding mothers who took metamizole within three months postpartum had a 2-fold increased risk of acute lymphoblastic leukemia in their children and a 3.87-fold increased risk of MLL gene rearrangement in infants under one year old. ◉ Effects on lactation and breast milk: As of the revision date, no relevant published information was found.

[1]. Inhibition of cyclooxygenases by dipyrone. Br J Pharmacol. 2007 Jun;151(4):494-503.

[2]. Therapeutic doses of nonsteroidal anti-inflammatory drugs inhibit osteosarcoma MG-63 osteoblast-like cells maturation, viability, and biomineralization potential. ScientificWorldJournal. 2013 Sep 19;2013:809891.

[3]. 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]. 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.

[5]. A Comparative Investigation of the Analgesic Effects of Metamizole and Paracetamol in Rats. J Invest Surg. 2015 Jun;28(3):173-80.

Metamizole sodium is the organic sodium salt of antipyrine, with a methyl (sulfonic acid methyl)amino group substituted at the C-4 position. It is commonly used as a potent analgesic and antipyretic. It possesses various pharmacological effects, including non-narcotic analgesia, antirheumatic drug, peripheral nervous system drug, antipyretic, prodrug, cyclooxygenase 3 inhibitor, and anti-inflammatory agent. It contains the methylaminopyrine (1-) structure. It is a drug with analgesic, anti-inflammatory, and antipyretic effects. It is sodium sulfonate of aminopyrine.

C13H18N3NAO5S

351.3528

333.075

5907-38-0

Metamizole sodium;68-89-3

522325

White to off-white solid powder

1.504

0

6

4

22

552

0

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

NSC 73205; NSC-73205; Dipyrone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

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

DMSO : ~100 mg/mL (~284.62 mM)
H2O : ≥ 100 mg/mL (~284.62 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.12 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: 100 mg/mL (284.62 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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