Involvement of opioid antagonists on COX-2 activity
1 Pharmacology Program, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, Universidad de Chile, Santiago, 8380453, Chile
2 oficina de Apoyo a la Investigación Científica (OAIC), Clinical Hospital, Universidad de Chile, Santiago, 8380453, Chile.
3 Medical School, Universidad de San Sebastián, Santiago, 8380453, Chile
4 Faculty of Medicine, Diego ¨Portales University, Santiago, 8380453, Chile
5 Faculty of Medicine, P. Universidad Católica, Santiago, 83809453, Chile.
6 Cardiovascular Department, Clinical Hospital, Universidad de Chile, Santiago, Chile.
Research Article
World Journal of Advanced Research and Reviews, 2023, 18(03), 1277–1282
Article DOI: 10.30574/wjarr.2023.18.3.1215
Publication history:
Received on 13 May 2023; revised on 24 June 2023; accepted on 26 June 2023
Abstract:
Pain is a complex process involving complex molecular and cellular mechanisms and pharmacotherapeutic strategies including nonsteroidal anti-inflammatory drugs (NSAIDs). The main mechanism of action of them, both for their adverse and therapeutic effects, is the inhibition of cyclooxygenases (COXs), one of its isoforms is COX-2 with selective inhibitors such as celecoxib, rofecoxib, and etoricoxib. The objective of this study was to evaluate the nociceptive interaction of COX-2 NSAIDs with other drugs due to the scarce information available in this regard. Antinociception was assessed by the formalin hind paw test evaluated from dose-response curves obtained before and after the i.p. administration of 1,0 mg/kg of naltrexone (NTX), or naltrindole (NTI), or nor-binaltorphimine (nor-BNI) in the assay, using at least 6-8 animals for each of at least 4 doses. Analgesic ratio (AR) expressed as the relation between ED50 of phase II / phase I of FHP indicates the following order of relative potency: celecoxib > parecoxib > etoricoxib. Administration of naltrexone or naltrindole induced a significant reduction of the analgesic activity of celecoxib, etoricoxib and parecoxib, reflected by an increase in the respective ED50 in both phases of FHP assay. However, norbinaltorphimine lack of effect. The results of the work demonstrate that opioid receptors MOR and DOR play a key role in coxib-induced antinociception in the FHP trial and while the KOR opioid receptor seems not to be involved in this antinociception.
Keywords:
Celecoxib; Naltrexone; Naltrindole; Nor-binaltorphimine; Formalin assay
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