Pharmacodynamic differences between racemic ibuprofen and dexibuprofen in murine preclinical study

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain, but their use is restricted by their adverse effects. In this study, the pharmacological profile of ibuprofen and dexibuprofen was evaluated using the murine acetic acid writhing test, and the participation of naltrexone, naltrindole, nor-binaltorphimine, L-NAME, risperidone, and tropisetron in the antinociceptive efficacy. Antinociception was assessed by dose–response curves to ibuprofen and dexibuprofen before and after the i.p. administration of 1,0 mg/kg of naltrexone, or naltrindole, or norbinaltorphimine, or 5 mg/kg of L-NAME, 0,5 mg/kg of risperidone, or tropisetron in the murine assay. Results are presented as means ± SEM and differences calculated by one-way ANOVA followed by Tukey's post-test. Ibuprofen and dexibuprofen produced a dose-dependent antinociceptive effect with different potency. After pretreatment of mice with naltrexone, naltrindole, nor-binaltorphimine, L-NAME, risperidone, or tropisetron, a significant increase in ibuprofen efficacy was obtained, however, no effect on dexibuprofen activity was obtained. Data demonstrate that ibuprofen and dexibuprofen induce effective antinociception in the acetic acid writhing test, either directly, through COX inhibition, or indirectly, through the modulatory effects of opioid or serotonin, or nitric oxide receptors. These actions are complex since the effects depending on the chemical structure of the NSAID. Thus, a racemic compound (ibuprofen) induces a significant increase in nociceptive efficacy. However, they have no effect on the dextrorotatory enantiomer (dexibuprofen).