Novel bioactive metabolites of dipyrone (metamizol)

Tobias Rogosch; Christian Sinning; Agnes Podlewski; Bernhard Watzer; Joel Schlosburg; Aron H. Lichtman; Maria G. Cascio; Tiziana Bisogno; Vincenzo Di Marzo; Rolf Nüsing; Peter Imming

doi:10.1016/j.bmc.2011.11.028

Novel bioactive metabolites of dipyrone (metamizol)

Tobias Rogosch, Christian Sinning, Agnes Podlewski, Bernhard Watzer, Joel Schlosburg, Aron H. Lichtman, Maria G. Cascio, Tiziana Bisogno, Vincenzo Di Marzo, Rolf Nüsing, Peter Imming^*

^*Corresponding author for this work

Medical Sciences

Research output: Contribution to journal › Article › peer-review

101 Citations (Scopus)

Abstract

Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB ₁ and CB ₂) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain.

Original language	English
Pages (from-to)	101-107
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	1
Early online date	25 Nov 2011
DOIs	https://doi.org/10.1016/j.bmc.2011.11.028
Publication status	Published - 1 Jan 2012

Bibliographical note

Funding Information:
The authors wish to thank Prof. Dr. Beat Lutz, Department of Physiological Chemistry, Johannes-Gutenberg-Universität Mainz, Germany, and Prof. Dr. Benjamin F. Cravatt, Department of Cell Biology, The Scripps Research Institute, La Jolla, California, for providing the FAAH knockout mice. The LC/MS studies were supported by DFG grant SE 263/17-1. AHL acknowledges support by National Institutes of Health Grants P01DA009789, P01DA017259, F31DA026279 and T32DA007027. We thank Sanofi-Aventis Deutschland GmbH, Berlin, Germany, for a gift of 2 and 3 .

Keywords

Analgesia
Arachidonic acid amides
Cannabinoid receptors
Cyclooxygenase
Dipyrone

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10.1016/j.bmc.2011.11.028

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abstract = "Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB 1 and CB 2) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain.",

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AU - Cascio, Maria G.

AU - Bisogno, Tiziana

AU - Di Marzo, Vincenzo

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Novel bioactive metabolites of dipyrone (metamizol)

Abstract

Bibliographical note

Keywords

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