Nimesulide exhibits a limited effect on COX-1 (IC50 >100 μM), but it is a selective inhibitor of COX-2 with IC50s ranging from 70 nM to 70 μM in a time-dependent manner[1]. In endometrial cancer cells, imimezolide (10 μM) significantly reduces VEGF, while having no effect on normal cells. Nimesulide (10 and 50 µM) significantly lowers MCP-1 levels in normal cells; 10 µM has the same effect on cancer cells. Moreover, mesulide (50 µM) has little effect on cancer cells but has a strong effect on the amount of IL-8 in normal cells[3].

In rats, imesulide (3 and 10 mg/kg, ip) significantly prevents fever brought on by an intraperitoneal injection of LPS. Nimesulide (3 mg/kg, ip) potently suppresses the fever response brought on by TNF-α, IL-1β, or IL-6, but it has no effect on the arachidonic acid-induced initial spike in the fever response. Additionally, mesulide dramatically lowers PGE2 and PGF2α levels in the brain fluid of rats treated with lipopolysaccharide (LPS) and 97% suppresses the rise in plasma TNF-α[2].

Absorption, Distribution and Excretion
Rapidly absorbed following oral administration.
Renal (50%), fecal (29%)

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Metabolism / Metabolites
Hepatic. Extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).

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Biological Half-Life
1.8–4.7 hours

Hepatotoxicity
Prospective studies show that up to 15% of patients taking NSAIDs experience at least transient serum aminotransferase elevations. A lower rate has been reported with nimesulide. These elevations are generally transient, mild and asymptomatic, and may resolve even with drug continuation. Marked aminotransferase elevations (>3 fold elevated) occur in
Likelihood score: A (well established cause of clinically apparent liver injury).

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Protein Binding
>97.5%

[1]. Effect of nimesulide action time dependence on selectivity towards prostaglandin G/H synthase/cyclooxygenase activity. Arzneimittelforschung. 1995 Oct;45(10):1096-8.

[2]. Nimesulide-induced antipyresis in rats involves both cyclooxygenase-dependent and independent mechanisms. Eur J Pharmacol. 2006 Aug 14;543(1-3):181-9.

[3]. The effect of COX-2 inhibitor, nimesulide, on angiogenetic factors in primary endometrial carcinoma cell culture. Clin Exp Med. 2007 Mar;7(1):6-10.

Nimesulide is an aromatic ether having phenyl and 2-methylsulfonamido-5-nitrophenyl as the two aryl groups. It has a role as a cyclooxygenase 2 inhibitor and a non-steroidal anti-inflammatory drug. It is a C-nitro compound, a sulfonamide and an aromatic ether. It is functionally related to a nitrobenzene.
Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. Due to concerns about the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries.
Nimesulide is a nonsteroidal antiinflammatory drug (NSAID) with relative specificity for COX-2 that is not available in the United States, but is used widely in other countries in the treatment of acute pain. Nimesulide has been linked to a low rate of transient serum enzyme elevations during therapy, but also to many instances of clinically apparent acute liver injury that can be severe and can result in acute liver failure, need for emergency liver transplantation and death.
Nimesulide is a nonsteroidal arylsulfonamide with anti-inflammatory properties. Nimesulide inhibits the cyclooxygenase-mediated conversion of arachidonic acid to pro-inflammatory prostaglandins. Modestly selective for COX-2, this agent binds to the enzyme, thereby inactivating it. Nimesulide may inhibit some carcinogenic COX-2-related carcinogenic effects on xenobiotic metabolism, apoptosis, immune surveillance and angiogenesis (overexpressed COX-2 in tumor epithelial cells enhances production of vascular growth factors and the formation of capillary-like networks). (NCI04)

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Drug Indication
For the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.

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Mechanism of Action
The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine.

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Pharmacodynamics
Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.

C13H12N2O5S

308.31

308.046

51803-78-2

Nimesulide-d5;1330180-22-7

4495

Light yellow to yellow solid powder

1.5±0.1 g/cm3

442.0±55.0 °C at 760 mmHg

140-146°C

221.1±31.5 °C

0.0±1.1 mmHg at 25°C

1.638

3.79

1

6

4

21

450

0

HYWYRSMBCFDLJT-UHFFFAOYSA-N

InChI=1S/C13H12N2O5S/c1-21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h2-9,14H,1H3

N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.11 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 (8.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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