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Anti‐inflammatory non steroidal drugs releasing NO (NO‐NSAIDs) are a new class of anti‐inflammatory drugs to which has been added an NO‐releasing moiety. These compounds have been shown to retain the anti‐inflammatory, analgesic and antipyretic activity of the parent compound but to be devoid of gastrointestinal (GI) toxicity.

Freund's adjuvant (FA) arthritis was induced in rats by a single intraplantar injection into the right hindpaw of 100 μl of mycobacterium butirricum (6 mg ml⁻¹). The effect of equimolar doses of naproxen (1, 3 and 10 mg kg⁻¹) and NO‐naproxen (1.5, 4.5 and 16 mg kg⁻¹) was evaluated using two dosage regimen protocols: (i) preventive, starting oral administration of the drugs at the time of induction of arthritis and for the following 21 days (day 1–21); (ii) therapeutic, starting oral administration of the drugs 7 days after adjuvant injection and for the following 14 days (day 7–21 …