Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Effects of metabolites of the analgesic agent dipyrone (metamizol) on rostral ventromedial medulla cell activity in mice.

Authors: Sabatino Maione, Lilyana Radanova, Danilo De Gregorio, Livio Luongo, Luciano De Petrocellis, Vincenzo Di Marzo, Peter Imming

Journal, date & volume: Eur. J. Pharmacol., 2015 Feb 5 , 748, 115-22

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25557763

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.