Nimesulide, a Nonsteroidal Anti-Inflammatory Drug, Displays Antianaphylactic and Antihistaminic Activity in Guinea-Pigs

Summary

The nonsteroidal anti-inflammatory compound nimesulide (4-nitro-2-phenoxymethane sulfonanilide) antagonises the effect of histamine and inhibits the release of this autacoid during immunological reaction in guinea-pigs. The antihistaminic activity of nimesulide, studied in isolated guinea-pig trachea, is specific for the H₁-receptor and is of a noncompetitive type. At a concentration of 1 × 10⁻⁵ mol/L, the potency of nimesulide is nearly half that of mepyramine (pyrilamine) at 1 × 10⁻⁶ mol/L. Furthermore, unlike indomethacin, nimesulide dose-dependently antagonises the effect of histamine on airway resistance of anaesthetised guinea-pigs. In actively ovalbumin-sensitised anaesthetised guinea-pigs, both nimesulide and indomethacin significantly protected the animals from the fatal systemic anaphylactic crisis. However, in perfused sensitised guinea-pig lungs, nimesulide reduced the anaphylactic release of histamine in a concentration-dependent way, whereas indomethacin, in spite of its inhibitory potency on thromboxane A₂ formation, potentiated the immune release of histamine. The bronchoconstriction induced by acetaldehyde, administered by aerosol (2.5% in saline) in sensitised anaesthetised guinea-pigs, was substantially reduced by both nimesulide and mepyramine administered by inhalation and by intravenous injection. These data further support the antihistaminic property of nimesulide and also suggest a possible interference of the compound with the degranulation process of sensitised mast cells in response to acetaldehyde. In conclusion, the capacity of nimesulide to control the immunological release of histamine and to attenuate its effect at the receptor level of the airway smooth muscles of the guinea-pig, may have some therapeutic relevance in patients with inflammation of the respiratory tract aggravated by intolerance to aspirin-like drugs.