Evaluation of the systemic and spinal antinociceptive effect of a new hybrid NSAID tetrahydropyran derivative

Clin Exp Pharmacol Physiol. 2021 Dec 4. doi: 10.1111/1440-1681.13617. Online ahead of print.ABSTRACTPain is responsible for inducing physical and mental stress, interfering negatively in patients' quality of life. Classic analgesic drugs, such as opioids and non-steroidal anti-inflammatory drugs, are known for their wide range of adverse effects, making it important to develop new drugs. Thus, this study aimed to analyze the action of the hybrid compound cis- (±) -acetate of 4-chloro-6- (naphthalene-1-yl) -tetrahydro-2h-pyran -2-yl) methyl2- (2- (2,6-dichlorophenylamine) phenyl (LS19) under acute nociceptive conditions, and deepened the understanding of the responsible mechanisms. Male swiss mice were evaluated in the acetic acid-induced abdominal writhing, formalin, tail-flick, capsaicin- and glutamate-induced nociception, thermal stimulation in animals injected with capsaicin and rotarod tests besides the acute and subchronic toxicological evaluation. The compound showed effect on the acetic acid-induced abdominal writhing, formalin (both phases), tail-flick, thermal stimulation in animals injected with capsaicin and capsaicin-induced nociception tests. In the study of the mechanism of action was observed reversion of the antihyperalgesic effect of the compound from the previous intraperitoneal and intrathecal administration of naloxone, nor-binaltorphimine, naltrindole, methylnaltrexone, 7-nitroindazole, L-NAME, ODQ, glibenclamide on the tail flick test. In the thermal st...
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Source Type: research