Metamizole-d3 (sodium salt)

Metamizole-d₃ is intended for use as an internal standard for the quantification of metamizole by GC- or LC-MS. Metamizole is a nonopioid prodrug that is rapidly hydrolyzed to the analgesic and antipyretic metabolites 4-methylaminoantipyrine (MAA) and 4-aminoantipyrine (AA).¹ It inhibits COX-1 and COX-2 activity (IC₅₀ = ~150 µg/ml for both in cell-free assays), as well as reduces increases in intracellular calcium levels induced by the TRPA1 agonist AITC in isolated rat and mouse dorsal root ganglia and IMR-90 human fibroblasts (IC₅₀s = 30-91 µM in patch-clamp assays).^2,3 Metamizole (6, 12, and 25 µg/ml) inhibits ADP- and epinephrine-induced platelet aggregation in human platelet-rich plasma (hPRP).⁴ It prevents fever induced by LPS, TNF-α, and IL-6, but not arachidonic acid or prostaglandin E₂ , in rats when administered at a dose of 120 mg/kg.⁵ Metamizole (250 and 500 mg/kg) increases the paw withdrawal threshold in the paw pressure test, indicating analgesic activity, in rat models of carrageenan-induced acute pain and postoperative incision pain.⁶

1.Rogosch, T., Sinning, C., Podlewski, A., et al.Novel bioactive metabolites of dipyrone (metamizol)Bioorg. Med. Chem.20(1)101-107(2012) 2.Campos, C., de Gregorio, R., GarcÍa-Nieto, R., et al.Regulation of cyclooxygenase activity by metamizolEur. J. Pharmacol. 378(3)339-347(1999) 3.Nassini, R., Fusi, C., Materazzi, S., et al.The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivativesBr. J. Pharmacol.172(13)3397-3411(2015) 4.Papp, J., Sandor, B., Vamos, Z., et al.Antiplatelet effect of acetylsalicylic acid, metamizole and their combination - in vitro and in vivo comparisonsClin. Hemorheol. Microcirc. 56(1)1-12(2014) 5.De Souza, G.E.P., Cardoso, R.A., Melo, M.C.C., et al.A comparative study of the antipyretic effects of indomethacin and dipyrone in ratsInflamm. Res. 51(1)24-32(2002) 6.Ince, I., Aksoy, M., Ahiskalioglu, A., et al.A comparative investigation of the analgesic effects of metamizole and paracetamol in ratsJ. Invest. Surg. 28(3)173-180(2015)