((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(methyl-d3)amino)methanesulfonate,monosodiumsalt

Description

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 (PGE₂; ）, 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

References

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 metamizol Eur. 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 derivatives Br. 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 comparisons Clin. 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 rats Inflamm. 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 rats J. Invest. Surg. 28(3),173-180(2015).