[Effect of traxanox sodium on SRS-A release in bronchial and peritoneal anaphylaxis].
The effect of traxanox on SRS-A release was examined in vivo and compared with that of disodium cromoglycate (DSCG). Intravenous antigen challenge produced an intense anaphylactic bronchoconstriction that showed a peak time of 5 min in egg albumin-sensitized guinea pigs pretreated with three agents, mepyramine (2.5 mg/kg, i.v.), indomethacin (1 mg/kg, i.v.) and propranolol (0.05 mg/kg, i.v.). This bronchoconstriction was almost completely inhibited by additional pretreatment with an SRS-A antagonist, FPL 55712 (2.5 mg/kg, i.v.). A lipoxygenase inhibitor, BW755C (10 mg/kg, i.v.), also significantly inhibited this reaction. These results indicate that this anaphylactic bronchoconstriction is due to the release of endogenous SRS-A. In this model, traxanox (5 and 10 mg/kg, i.v.) showed a dose-related inhibition, but DSCG (10 mg/kg, i.v.) did not. FPL 55712 (1 mg/kg, i.v.) administered at the peak time of the bronchoconstriction caused a relaxation. Traxanox, on the other hand, failed to relax this reaction. In IgE-mediated rat passive peritoneal anaphylaxis (PPA), traxanox (0.01--10 micrograms/rat, i.p.) inhibited the release of SRS-A and histamine dose-dependently. This inhibitory effect was about 10--20 times as potent as that of DSCG. In addition, both traxanox (0.1 microgram/rat, i.p.) and DSCG (1 microgram/rat, i.p.) showed a synergistic effect in combination with isoproterenol (0.01 microgram/rat, i.p.) and an additive effect with theophylline (100 micrograms/rat, i.p.) in inhibiting the release of SRS-A in rat PPA. These results suggest that traxanox inhibits the release of SRS-A in vivo, so that it may be clinically effective in treating patients with allergic bronchial asthma.
D000707:Anaphylaxis / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010529:Peritoneal Cavity; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism*
D002867:Chromones; D006634:Histamine H1 Antagonists; D013189:SRS-A; D011433:Propranolol; C020178:traxanox; D011738:Pyrilamine; D007545:Isoproterenol; D004205:Cromolyn Sodium