New analogues oxyethylariamides of canabidiol with anti-inflammatory properties

Currently, medicinal chemists are searching for new molecules that are analogous to cannabidiol due to its therapeutic effects in diseases such as epilepsy, and its anti-inflammatory, analgesic and non-psychotropic properties. Therefore, the objective of this study is to evaluate the anti-inflammatory and/or antinociceptive effects of three new oxyethylamides of cannabidiol (PQM-337, PQM-338 and PQM-343). Swiss Webster mice (28-32 g, n=6-8) were used in acute toxicity and formalin-induced paw licking models. Animals received the highest dose of the substances (10 µmol/kg) orally and after 24h were euthanized for blood collection, weighing of specific organs and collection of bone marrow lavage. The formalin-induced paw licking model consists of evaluating two distinct phases, the 1st phase related to neurogenic pain (0-5 min) and the 2nd phase related to inflammatory pain (15-30 min) and the sum of the licking time of each phase is counted. Thus, the animals were orally pretreated with 10 µmol/kg of each PQM. After 1 hour, 20 µL of formalin (2.5%) was injected intraplantarly into the hind paw of each animal. The results were expressed as mean ±SD. Statistical analysis was performed by ANOVA followed by the Tukey test (*p<0.05). The protocol for the use of animals was approved by CEUA/UFRJ and received the numbers 31/19 and 28/20. None of the substances showed changes in hematological parameters, difference in organ weight or bone marrow toxicity, when compared to the control group. In the formalin model, PQMs reduced the time of licking paw only in the 2^nd phase, as demonstrated by the results: vehicle: 259.7±22.3sec; ASA (1110 µmol/kg): 63.2±15.9*sec.; morphine (6,5 µmol/kg): 141±19*sec.; PQM-337: 134.4±21.5*sec.; PQM-338: 151.5±17.9*sec.; PQM-343: 131.0±35.4* sec. The preliminary results suggest that all substances tested did not demonstrate acute toxicity and present an anti-inflammatory activity profile in an acute model of nociception and inflammation.