title: Effects of metabolites of the analgesic agent dipyrone (metamizol) on rostral ventromedial medulla cell activity in mice.
abstract: The molecular mechanism of action of dipyrone, a widely used antipyretic and non-opioid analgesic drug, is still not fully understood. Actions upon peripheral inflamed tissues as well as the central nervous system, especially upon the PAG-RVM axis, have been suggested. Dipyrone is a prodrug and its activity is due to its immediate conversion to its active metabolites. We tested the effect of two recently discovered metabolites of dipyrone, the arachidonoyl amides of 4-methylaminoantipyrine and 4-aminoantipyrine, on the neurons of the rostral ventromedial medulla (RVM), which are part of the descending pathway of antinociception. These compounds reduced the activity of ON-cells and increased the activity of OFF-cells. Both CB1 and TRPV1 blockade reversed these effects, suggesting that the endocannabinoid/endovanilloid system takes part in the analgesic effects of dipyrone.
authors.affiliation: Endocannabinoid Research Group at the Department of Experimental Medicine, Division of Pharmacology "L. Donatelli", The Second University of Naples, 80138 Naples, Italy.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.affiliation: Institut fuer Pharmazie, Martin-Luther-Universitaet Halle, Germany.
authors.forename: Lilyana
authors.initials: L
authors.lastname: Radanova
authors.affiliation: Endocannabinoid Research Group at the Department of Experimental Medicine, Division of Pharmacology "L. Donatelli", The Second University of Naples, 80138 Naples, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: De Gregorio
authors.affiliation: Endocannabinoid Research Group at the Department of Experimental Medicine, Division of Pharmacology "L. Donatelli", The Second University of Naples, 80138 Naples, Italy.
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.affiliation: Endocannabinoid Research Group at the Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.affiliation: Endocannabinoid Research Group at the Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (NA), Italy. Electronic address: vdimarzo@icb.cnr.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.affiliation: Institut fuer Pharmazie, Martin-Luther-Universitaet Halle, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Imming
mesh_terms: D000700:Analgesics / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D004177:Dipyrone / Q000378:metabolism* / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D004347:Drug Interactions; D005110:Extracellular Space / Q000187:drug effects; D008297:Male; D055595:Mechanical Phenomena; D008636:Mesencephalon / Q000166:cytology*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
chemical_list: D000700:Analgesics; D004224:Diterpenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C468130:iodoresiniferatoxin; D016718:Arachidonic Acid; C103505:AM 251; D004177:Dipyrone
keywords: Analgesia; Arachidonic acid amides; Dipyrone; Periaqueductal gray; Rostral ventromedial medulla