Salicytamide: a New Anti-inflammatory Designed Drug Candidate
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Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test’s inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test’s neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10–25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.
KEY WORDSantinociception antioedematogenic paracetamol acetylsalicylic acid salicytamide
KMMG and SCC were supported by a Brazilian Government/Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) fellowship. RSB is supported by a research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Compliance with Ethical Standards
All procedures were approved by the Ethics Committee on Experimental Animals of the Federal University of Pará under license number FAR 001-10-CEPAE/UFPA. The number of animals and the intensity of noxious stimuli were standardized according to the ethical guidelines for the investigation of experimental pain in conscious animals (Zimmermann, 1983) and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines .
Conflict of Interest
The authors declare that they have no conflict of interest.
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