Nitroparacetamol exhibits anti‐inflammatory and anti‐nociceptive activity

• Published in: British journal of pharmacology Vol. 130; no. 7; pp. 1453 - 1456
• Main Authors: Al‐Swayeh, O A, Futter, L E, Clifford, R H, Moore, P K
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2000; Nature Publishing
• Subjects: Acetaminophen - analogs & derivatives; Acetaminophen - therapeutic use; acetic acid; Analgesics; Analgesics - therapeutic use; Analysis of Variance; Animals; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; carboxymethylcellulose; Carrageenan; Edema - chemically induced; Edema - prevention & control; hyperalgesia; Male; Medical sciences; Neuropharmacology; Nitroparacetamol; oedema; Pain - prevention & control; Pain Measurement - drug effects; paracetamol; Pharmacology. Drug treatments; Rats; Rats, Wistar; Special Report; Nitro compound; Edema; Cellulose(carboxymethyl); Intraperitoneal administration; Rat; Rodentia; Antiinflammatory agent; Oral administration; Biological activity; Hyperalgesia; Vertebrata; Paracetamol; Mammalia; Analgesic; Mouse; Animal; Nitric oxide; Carrageenan; Acetic acid
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703509

Nitroparacetamol (NCX‐701) is a newly synthesized nitric oxide‐releasing derivative of paracetamol. Following i.p. administration, nitroparacetamol inhibits carrageenan‐induced hindpaw oedema formation (ED50, 169.4 μmol kg−1) and mechanical hyperalgesia (ED50, 156 μmol kg−1) in the rat. In contrast, the parent compound, paracetamol, exhibits no significant anti‐oedema activity in this model (ED50>1986 μmol kg−1, i.p.) and is markedly less potent than nitroparacetamol as an inhibitor of carrageenan‐mediated hyperalgesia (ED50, 411.6 μmol kg−1, i.p.). In a second model of nociception (inhibition of acetic acid induced abdominal constrictions in the mouse), nitroparacetamol administered orally (ED50, 24.8 μmol kg−1), was again considerably more potent than paracetamol (ED50, 506 μmol kg−1, p.o.). Thus, compared with paracetamol, nitroparacetamol not only exhibits augmented antinociceptive activity in both rat and mouse but, intriguingly, is also anti‐inflammatory over a similar dose range. British Journal of Pharmacology (2000) 130, 1453–1456; doi:10.1038/sj.bjp.0703509