부산대학교 도서관

Molecular modification of compounds remains important strategy towards the discovery of new drugs. In this sense, this study presents a new pyrazole derivative 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole (LQFM039) and evaluated the antiinflammatory, analgesic, and vasorelaxant effects of this compound as well the mechanisms of action involved in the pharmacological effects. For this, mice were orally treated with LQFM039 (17.5, 35, or 70mg/kg) prior acetic acid-induced abdominal writhing, formalin, tail flick, and carrageenan-induced paw edema protocols. In addition, vascular reactivity protocols were made with aortic rings contraction with phenylephrine and stimulated with graded concentrations of LQFM039. Abdominal writhing and licking time in both neurogenic and inflammatory phases of formalin were reduced with LQFM039 without altering latency to nociceptive response in the tail flick test. Carrageenan-induced paw edema showed that LQFM039 reduces edema and cell migration. In addition, the mechanism of action of LQFM039 involves NO/cGMP pathway and calcium channels, since this new pyrazole derivate elicited concentration-dependent relaxation attenuated by N[omega]-nitro-L-arginine methyl ester and 1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one, and blockade of Ca[Cl.sup.2]-induced contraction. Altogether, our finding suggests anti-inflammatory, antinociceptive, and vasorelaxant effect of this new pyrazole derivative with involvement of NO/cGMP pathway and calcium channels. Key words: LQFM039, potassium channels, calcium channels, NO/GMPc Pathway
Introduction Inflammation is an essential physiological response and host defense strategy to injury of living tissues; however, it can lead to organ failure or death (Kumar et al. 2004). The [...]