ACEMETACIN ANTINOCICEPTIVE MECHANISM IS NOT RELATED TO NO OR K+ CHANNEL PATHWAYS
Ortiz Ramírez, Mario Isidoro
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Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of acute gout and inflammation. However, its use is limited due to side effects. Acemetacin is a prodrug of indomethacin that exhibits better gastric tolerability in preclinical and clinical trials. The aim of this study was to examine if the systemic administration of acemetacin involved the sequential participation of nitric oxide (NO) or K+ channel pathways to confer its antinociceptive effect, as compared to indomethacin. The antinociceptive effect of both drugs was studied with the formalin test. Equimolar doses of acemetacin or indomethacin were administered orally. The intraplantar administration of either L-NAME, glibenclamide, apamin or charybdotoxin plus indomethacin or acemetacin was studied using the formalin test and the anti-inflammatory and antihyperalgesic effects were measured. The antinociceptive effect of acemetacin or indomethacin was not significantly different when pretreatment with L-NAME, glibenclamide, apamin or charybdotoxin was done. The antihyperalgesic and antiinflammatory effects were also similar for both indomethacin and acemetacin. Our results suggest that the antinociceptive effect of indomethacin or acemetacin is not mediated by NO or K+ channel activation.