[Effect of traxanox sodium on SRS-A release in bronchial and peritoneal anaphylaxis].

Abstract

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.

• Authors: M Terasawa, T Imayoshi, K Goto
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 82 Issue 1 Pg. 93-101 (Jul 1983) ISSN: 0015-5691 [Print] Japan
• PMID: 6194083 (Publication Type: Journal Article)

Chemical References

• Chromones
• Histamine H1 Antagonists
• SRS-A
• Propranolol
• traxanox
• Pyrilamine
• Isoproterenol
• Cromolyn Sodium

Topics

• Anaphylaxis (metabolism)
• Animals
• Bronchi (drug effects, metabolism)
• Chromones (pharmacology)
• Cromolyn Sodium (pharmacology)
• Female
• Guinea Pigs
• Histamine H1 Antagonists (pharmacology)
• Histamine Release (drug effects)
• Isoproterenol (pharmacology)
• Male
• Muscle Contraction (drug effects)
• Peritoneal Cavity
• Propranolol (pharmacology)
• Pyrilamine (pharmacology)
• Rats
• Rats, Inbred Strains
• SRS-A (metabolism)