Metamizole sodium

Metamizole sodium is a non-opioid compound with excellent analgesic and antipyretic effects. Metamizole (sodium) is a cyclooxygenase-3 (COX-3) inhibitor[1][2].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Immunology/Inflammation >> COX

Research Areas >> Neurological Disease

COX-3[2]

Metamizole sodium inhibits COX-3 with IC50 value of 52 μM and COX-1 at a 6.6-fold higher concentration in insect cells[2]. Metamizole (1-500 μM; 48 hours) significantly inhibits cell proliferation in pancreatic cancer cells[3]. Cell Proliferation Assay[3] Cell Line: Pancreatic cancer cell lines PaTu 8988t and Panc-1 Concentration: 1 μM, 10 μM, 100 μM, 250 μM, 500 μM Incubation Time: 48 hours Result: Significantly inhibited cell proliferation in the PaTu 8988t cell line; significantly inhibited cell proliferation in the pancreatic cancer cell line Panc-1 at 1-250 μM.

Metamizole sodium (500 mg/kg; i.p.; twice a day; for 7 days) diminishes the development of neuropathic pain symptoms in rats[4]. Animal Model: Male Wistar rats (270-300 g), with peripheral neuropathic pain[4] Dosage: 500 mg/kg Administration: Intraperitoneal injection, twice a day, for 7 days Result: Diminished the expression of pronociceptive interleukins (IL-1beta, IL-6, and IL-18) and chemokines (CCL2, CCL4, and CCL7) in DRG measured 7 days after sciatic nerve injury.

[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.

MOLECULAR FORMULA :

C13-H17-N3-O4-S.Na

MOLECULAR WEIGHT :

334.38

WISWESSER LINE NOTATION :

T5NNVJ A1 BR& D1M1SWQ E1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LC - Lethal concentration

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>900 mg/m3

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2470 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2117 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2182 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1625 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2891 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LC50 - Lethal concentration, 50 percent kill

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

37200 mg/m3

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

250 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

69 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2197 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Unreported

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2750 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

2150 mg/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay) Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

61800 mg/kg/30D-I

TOXIC EFFECTS :

Endocrine - changes in spleen weight Blood - pigmented or nucleated red blood cells Blood - changes in leukocyte (WBC) count

TYPE OF TEST :

TCLo - Lowest published toxic concentration

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

192 mg/m3/4H/30D-I

TOXIC EFFECTS :

Behavioral - alteration of classical conditioning Liver - liver function tests impaired

TYPE OF TEST :

TCLo - Lowest published toxic concentration

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

20 mg/m3/4H/17W-I

TOXIC EFFECTS :

Brain and Coverings - recordings from specific areas of CNS Blood - change in clotting factors Nutritional and Gross Metabolic - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

45500 mg/kg/13W-C

TOXIC EFFECTS :

Liver - other changes Kidney, Ureter, Bladder - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

60 gm/kg/30D-C

TOXIC EFFECTS :

Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

60 gm/kg/30D-C

TOXIC EFFECTS :

Blood - normocytic anemia Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

6300 mg/kg/30D-I

TOXIC EFFECTS :

Endocrine - other changes Blood - changes in other cell count (unspecified)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

536 mg/kg/78W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

792 mg/kg/78W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Liver - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

30 mg/kg

SEX/DURATION :

lactating female 41 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other neonatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

750 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1 gm/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Cytogenetic analysis

MUTATION DATA

TYPE OF TEST :

Cytogenetic analysis

TEST SYSTEM :

Rodent - hamster Fibroblast

DOSE/DURATION :

750 mg/L

REFERENCE :

ESKHA5 Eisei Shikenjo Hokoku. Bulletin of the Institute of Hygienic Sciences. (Kokuritsu Eisei Shikenjo Kagaku, 18-1 Bushitsu Johobu, Setagaya-ku, Tokyo 158, Japan) V.1- 1886- Volume(issue)/page/year: (96),55,1978 *** OCCUPATIONAL EXPOSURE LIMITS *** OEL-RUSSIA:STEL 0.5 mg/m3 JAN 1993