Antagonism of histamine and leukotrienes by azelastine in isolated guinea pig ileum.
The effects of azelastine on histamine- and leukotriene C4 and D4 (LTC4, LTD4)-induced contractile responses in isolated guinea pig ileum were investigated. Following a 2-min contact with the ileum, azelastine produced competitive antagonism of histamine (pA2 = 8.24). Following a 15-min contact, azelastine at 2.5 X 10(-9) M exerted competitive antagonism, but at higher concentrations (10, 40 and 160 X 10(-9) M) it not only shifted histamine concentration-effect curves to the right but also suppressed its maximum. Thus, azelastine exerts a dual (competitive/noncompetitive) antagonism of histamine depending upon the concentration and duration of contact. Azelastine and FPL 55712 (a known LT receptor antagonist) produced concentration-dependent antagonism of LTC4 and LTD4. Azelastine and compound FPL 55712 also exerted concentration-dependent reversal (relaxation) of pre-existing LTC4-induced contractions. In conclusion, the potent H1-histamine and leukotriene receptor blocking activities of azelastine may contribute to its antiasthmatic/antiallergic activities.
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D006168:Guinea Pigs; D006633:Histamine Antagonists; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors*
D002867:Chromones; D006633:Histamine Antagonists; D010793:Phthalazines; D011724:Pyridazines; D013189:SRS-A; C006312:FPL 55712; C020976:azelastine