Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen.
Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity.
Cuzzolin
L
L
Institute of Pharmacology, University of Verona, Italy.
Conforti
A
A
Adami
A
A
Lussignoli
S
S
Menestrina
F
F
Del Soldato
P
P
Benoni
G
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002351:Carrageenan; D004064:Digestive System / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D008297:Male; D009288:Naproxen / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D002351:Carrageenan; C094069:nitronaproxen