Pharmacological studies on nitro‐naproxen (naproxen‐2‐nitrooxyethylester)

Naproxen-2-nitrooxyethylester (S-(+)-2-(6-methoxy-2-naphthyl)propanoic acid-2-nitrooxyethylester, LE-EK06) was synthesized from naproxen and 2-nitrooxyethylbromide as a novel nitric oxide–releasing derivative of naproxen. Molar equivalents of LE-EK06 (6.93–27.73 mg/kg, p.o.) to naproxen dose-dependently exhibited greater antinociceptive activity in comparison to naproxen in a writhing assay. The compound (5.54–22.18 mg/kg, p.o.) showed greater anti-inflammatory activity at 2 h after as comparable to its effect at 4 h after carrageenan challenge in rats. Further, LE-EK06 (9.45 mg/kg, p.o.) was more potent in the carrageenan-evoked hyperalgesia. LE-EK06 (11.09 mg/kg, p.o.) and naproxen (8.0 mg/kg, p.o.) showed a comparable inhibitory effect on exudate formation and migration of polymorphonuclear leukocytes (PMNs) in a carrageenan-induced pleurisy test. Further, the compound (11.09 mg/kg, p.o.) significantly reduced myeloperoxidase activity in carrageenan-treated paw and demonstrated significantly less gastrotoxicity in acute and chronic (21 days) studies. The scanning electron microscopy revealed that LE-EK06 showed only mild gastric damage (slight disruption of mucus layer) in comparison to naproxen. The present study suggested that naproxen-2-nitrooxyethylester (LE-EK06) represents a novel gastric sparing NSAID. Drug Dev. Res. 61:66–78, 2004. © 2004 Wiley-Liss, Inc.