Nitroparacetamol exhibits anti-inflammatory and anti-nociceptive activity

Abstract

Nitroparacetamol (NCX-701) is a newly synthesized nitric oxide-releasing derivative of paracetamol. Following i.p. administration, nitroparacetamol inhibits carrageenan-induced hindpaw oedema formation (ED(50), 169.4 micromol kg(-1)) and mechanical hyperalgesia (ED(50), 156 micromol kg(-1)) in the rat. In contrast, the parent compound, paracetamol, exhibits no significant anti-oedema activity in this model (ED(50)>1986 micromol kg(-1), i.p. ) and is markedly less potent than nitroparacetamol as an inhibitor of carrageenan-mediated hyperalgesia (ED(50), 411.6 micromol kg(-1), i.p.). In a second model of nociception (inhibition of acetic acid induced abdominal constrictions in the mouse), nitroparacetamol administered orally (ED(50), 24.8 micromol kg(-1)), was again considerably more potent than paracetamol (ED(50), 506 micromol 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.

Figure 1

Rats were administered paracetamol (A) or nitroparacetamol (B) 15 min before intraplantar carrageenan. Doses shown are mg kg⁻¹ (i.p.). Hindpaw oedema (ml) was measured by plethysmography. Results shown mean±s.e.mean, n=5–24, ^*P<0.05.

Figure 2

Inhibition of acetic acid induced abdominal constrictions in the mouse by paracetamol (A) and nitroparacetamol (B). Doses shown are mg kg⁻¹ (i.p.). Control animals received an appropriate volume of vehicle. Results shown mean±s.e.mean, n=10, ^*P<0.05.

Figure 3

Inhibition of mechanical hyperalgesia by paracetamol and nitroparacetamol. Drugs (mg kg⁻¹, i.p.) were administered 2.5 h after intraplantar carrageenan injection. Results show mean±s.e.mean, n=8.