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Pharmacological interaction between NSAIDS with clomipramine and risperidone in mice visceral pain
Author(s) -
Vargas Claudio Gonzalez,
Miranda Hugo F.,
Sierralta Fernando,
Noriega Viviana,
Prieto Juan Carlos
Publication year - 2019
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21519
Subject(s) - pharmacology , piroxicam , ketoprofen , nimesulide , potency , nociception , analgesic , medicine , chemistry , receptor , in vitro , biochemistry , alternative medicine , pathology
Nonsteroidal anti‐inflammatory drugs (NSAIDs) possess as primary action mechanism the inhibition of cyclooxygenases (COX‐1, COX‐2, and COX‐3), thus producing a decreasing prostaglandin synthesis. This study was designed to evaluate whether the antinociception induced by NSAIDs could be modulated by clomipramine or risperidone using a chemical model of inflammatory acute visceral pain, the abdominal acetic acid induced a writhing test in mice. Dose–response curves, intraperitoneal, or intrathecal for the antinociceptive activity displayed by ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol were analyzed in order to obtain the ED 50 of each drug. Pretreatment of mice with either clomipramine or risperidone, increased antinociceptive potency of ketoprofen, piroxicam, nimesulide, parecoxib, and paracetamol, expressed by a decrease in the values of antinociceptive ED 50. The results that were obtained are in line with those where the inhibition of COXs provides a justification for most of the pharmacological actions. Nevertheless, several findings suggest other molecular mechanisms, among which may be mentioned, L‐selecting shedding; inhibition of i‐NOS; inhibition of NF‐Kappa B; suppression metaloproteinasas; inhibition of ß2 integrin activation; activation of α 2 ‐adrenoceptor; increase of IL‐1ß; upregulation IL‐6. In conclusion, the data generated in this study demonstrated that risperidone and clomipramine, separately, increase antinociceptive potency of NSAIDs in a chemical model of inflammatory acute visceral tonic pain.