Dipyrone is a non-steroidal anti-inflammatory drug (NSAID) used primarily as an analgesic and antipyretic. Some hypothesize that dipyrone activity can modulate other pathways, including endocannabinoid signaling. Thus, the aim of this study was to evaluate the possible role of endocannabinoids in mediating dipyrone activity. This study will be based on the tetrad effects of cannabinoids, which are an antinoceptive and cataleptic state, hypolocomotion, and hypothermia. Dipyrone treatment caused a decrease in locomotor activity, increased the latency to a thermal analgesic response, and induced a cataleptic and hypothermic state. These reactions are similar to the tetrad effects caused by the cannabinoidagonist, WIN 55,212-2. CB1 receptor antagonist reversed dipyrone’s effects on locomotor activity, the cataleptic response and thermal analgesia. CB1 and TRPV1 antagonists accentuated the reduction in body temperature caused by dipyrone. However, CB2 antagonists did not alter the dipyrone-stimulated hypothermia response. These results indicate involvement of the endocannabinoid system, especially the CB1 receptor, in analgesia and the cataleptic effect and hypolocomotion. However, CB and TRPV1 receptors were not involved in hyporthermic effects. We hypothesize that dipyrone’s mechanism of action may involve COX and FAAH inhibition, which together provide additional arachidonic acid as substrate for endocannabinoid synthesis or other related molecules. This increase in endocannabinoid availability enhances CB1 receptor stimulation, contributing to the observed effects. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.