Antianaphylactic and antihistaminic activity of the non-steroidal anti-inflammatory compound nimesulide in guinea-pig.
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)
Berti
F
F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Rossoni
G
G
Buschi
A
A
Robuschi
M
M
Villa
L M
LM
D000403:Airway Resistance / Q000187:drug effects; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis; D014132:Trachea / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006634:Histamine H1 Antagonists; D013449:Sulfonamides; D013928:Thromboxane A2; D006632:Histamine; C012655:nimesulide; D007213:Indomethacin