Antianaphylactic and antihistaminic activity of the non-steroidal anti-inflammatory compound nimesulide in guinea-pig

Arzneimittelforschung. 1990 Sep;40(9):1011-6.


Nimesulide (4-nitro-2-phenoxymethane sulfonanilide, Aulin, Mesulid) is a non-steroidal anti-inflammatory compound which shows antihistaminic activity and inhibits the immune release of histamine. The antihistaminic activity of this compound is specific for H1-receptor and has been demonstrated on isolated strips of guinea-pig trachea and on histamine-induced multiphasic inotropic response in left atria of guinea pig electrically driven. The effect of nimesulide is of non competitive type and, at the concentration of 1 x 10(-5) mol/l, is nearly 2 time less potent than pyrilamine (mepyramine) at 1 x 10(-6) mol/l. Nimesulide (1.6 mumol/kg i.v.) inhibits both bronchoconstriction (69%) and TXB2 formation (93%) induced by histamine (0.05 mumol/kg i.v.) in anaesthetized guinea-pigs. In contrast indomethacin (1.6 mumol/kg i.v.) decreases the generation of TXB2 (89%) without affecting the enhancement in tracheal insufflation pressure induced by histamine. In actively sensitized guinea-pigs both nimesulide and indomethacin protect the animals from deadly anaphylactic crisis. The rise in tracheal pressure induced by the antigenic challenge is inhibited of 80% and 63% respectively by nimesulide and indomethacin (6.4 mumol/kg i.v.). At this dose the two compounds reduced of 90% approximately the immunological release of TXB2 in the circulation. The release of histamine, induced by the anaphylactic reaction caused in perfused lungs obtained from actively sensitized guinea-pigs, is lessened by nimesulide (EC50 = 3.06; fid. lim. 2.59-3.63 mumol/l) and potentiated by indomethacin (EC50 = 0.89; fid. lim. 0.67-1.17 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Airway Resistance / drug effects
  • Anaphylaxis / drug therapy*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aorta, Thoracic / drug effects
  • Blood Pressure / drug effects
  • Guinea Pigs
  • Histamine / pharmacology
  • Histamine H1 Antagonists*
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Lung / drug effects
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Myocardial Contraction / drug effects
  • Rabbits
  • Sulfonamides / pharmacology*
  • Thromboxane A2 / biosynthesis
  • Trachea / drug effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Histamine H1 Antagonists
  • Sulfonamides
  • Thromboxane A2
  • Histamine
  • nimesulide
  • Indomethacin