Pharmacodynamic differences between racemic ibuprofen and dexibuprofen in murine preclinical study
1 Pharmacology Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, 8380453, Chile.
2 Faculty of Medicine, Clinica Alemana, University of Desarrollo, Santiago, 6681920, Chile.
3 Scientific Research Support Office (OAIC), Clinical Hospital, University of Chile, Santiago, 8380453, Chile.
4 Faculty of Medicine, P. Universidad Católica, Santiago, 83809453, Chile.
5 Cardiovascular Department, Clinical Hospital, University of Chile, Santiago, 8380453, Chile.
Research Article
International Journal of Frontiers in Chemistry and Pharmacy Research, 2023, 03(02), 001–007.
Article DOI: 10.53294/ijfcpr.2023.3.2.0051
Publication history:
Received on 14 August 2023; revised on 25 September 2023; accepted on 27 September 2023
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).
Keywords:
Ibuprofen; Dexibuprofen; Writhing test; Antinociception
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