Inhibition of leukotriene (SRS-A)-mediated acute lung anaphylaxis by azelastine in guinea pigs.
Azelastine hydrochloride, chemically known as 1(2H)-phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepine-4-yl)-, monohydrochloride, is a novel, orally effective, long-acting, antiallergic/antiasthmatic agent. The ability of azelastine and selected antiallergic drugs to inhibit SRS-A (leukotriene)-mediated acute lung anaphylaxis in guinea pigs (Konzett-Rossler method) was investigated. Azelastine and ketotifen were administered p.o. 2 and 24 h before antigen challenge; disodium cromoglycate (DSCG) was administered i.v. immediately before antigen challenge. The oral dose of azelastine required to inhibit leukotriene-mediated allergic bronchospasm by 50% (ID50: mg/kg) was 0.063 at 2 h and 0.120 at 24 h. Ketotifen at a dose of 0.05 to 10 mg/kg at 2 and 24 h, p.o., as well as DSCG at a dosage of 0.3 to 10 mg/kg at 0 min, i.v., produced weak, inconsistent and nondose-related antianaphylactic effects. Azelastine is an orally effective and long-acting inhibitor of in vivo synthesis and/or release of leukotrienes.
D000707:Anaphylaxis / Q000517:prevention & control*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D013189:SRS-A / Q000037:antagonists & inhibitors*
D002867:Chromones; D010793:Phthalazines; D011724:Pyridazines; D013189:SRS-A; D001285:Atropine; C006312:FPL 55712; D011738:Pyrilamine; D004205:Cromolyn Sodium; D007665:Ketotifen; D007213:Indomethacin; D008784:Methysergide; C020976:azelastine