Antinociceptive Effect of a Novel Tosylpyrazole Compound in Mice

Abstract

Abstract: Pain is the most common complaint in the medical field and the identification of compounds that can effectively treat painful states without induction of side‐effects remains a major challenge in biomedical research. The aim of the present study was to investigate the antinociceptive effect of a novel compound, 3‐(4‐fluorophenyl)‐5‐trifluoromethyl‐1 H ‐1‐tosylpyrazole (compound A) in several models of pain in mice and compare with those produced by the known trifluoromethyl‐containing pyrazole compound celecoxib. Compound A or celecoxib were administrated by oral (78–780 µmol/kg), intrathecal (9–22.5 nmol/site) or intracerebroventricular (9–22.5 nmol/site) routes. Oral administration of either compound A or celecoxib abolished the mechanical allodynia, but not the oedema caused by intraplantar injection of carrageenan. Similarly, compound A reduced the overt nociception, but not the oedema, produced by bradykinin or capsaicin. However, compound A (500 µmol/kg, orally) did not alter nociception nor oedema caused by intraplantar injection of prostaglandin E 2 or glutamate, whereas celecoxib reduced only the nociception induced by the former. Moreover, oral and intrathecal administration of compound A or celecoxib also reduced the nociception induced by acetic acid. However, only celecoxib reduced the acetic acid‐induced nociception when it was injected by the intracerebroventricular route. Finally, neither compound A nor celecoxib was able to produce antinociceptive effect in the tail‐flick test or to alter the motor performance and the body temperature. Besides, compound A or celecoxib did not induce gastric lesion. Thus, compound A seems to be an interesting prototype for the development of novel analgesic drugs.