Nitroparacetamol exhibits anti-inflammatory and anti-nociceptive activity

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 mu mol kg(-1)) and mechanical hyperalgesia (ED50, 156 mu mol kg(-1)) in the rat. In contrast, the parent compound, paracetamol, exhibits no significant anti-oedema activity in this model (ED50>1986 mu mol kg(-1) i.p.) and is markedly less potent than nitroparacetamol as an inhibitor of carrageenan-mediated hyperalgesia (ED50, 411.6 mu mol 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 mu mol kg(-1)), was again considerably more potent than paracetamol (ED50, 506 mu mol kg(-1), p.o.). Thus, compared with paracetamol, nitroparacetamol not only exhibits augmented antinociceptive activity in both rat and mouse but, intriguingly, is also antiinflammatory over a similar dose range.