Interference by the novel PAF-acether antagonist WEB 2086 with the bronchopulmonary responses to PAF-acether and to active and passive anaphylactic shock in guinea-pigs.

Abstract

The interaction between the triazolothienodiazepine WEB 2086 and the in vitro and in vivo bronchopulmonary effects of PAF-acether and active/passive anaphylaxis in the guinea-pig was studied. WEB 2086 (1-100 nM) inhibited PAF-acether (10-100 ng)-induced bronchoconstriction and TXB2 release from isolated and perfused guinea-pig lungs without affecting the response to 100 micrograms arachidonic acid. In addition, 1-10 microM WEB 2086 significantly reduced antigen-induced TXB2 and histamine release from lungs from actively and passively sensitized guinea-pigs. In the presence of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), mepyramine, methysergide, indomethacin and atropine, WEB 2086 (20-50 microM) inhibited by 30-40% the residual contraction of lung parenchyma strips from guinea-pigs actively sensitized by 0.1-10 micrograms antigen. In vivo, WEB 2086 (0.1-1 mg/kg) reversed or abolished the bronchoconstriction, hypotension, thrombocytopenia and leukopenia evoked by perfusion of PAF-acether (3 or 44 ng/kg per min). At 3 mg/kg, WEB 2086 also markedly decreased the bronchoconstriction and leukopenia induced by 100 micrograms/kg antigen in mepyramine (5 micrograms/kg)-treated passively sensitized guinea-pigs. In contrast, WEB 2086 was ineffective against active anaphylaxis in vivo. These results demonstrate that WEB 2086 antagonizes the bronchopulmonary effects due to PAF-acether and to anaphylactic shock in the guinea-pig.

• Authors: M Pretolani, J Lefort, E Malanchère, B B Vargaftig
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 140 Issue 3 Pg. 311-21 (Aug 21 1987) ISSN: 0014-2999 [Print] Netherlands
• PMID: 3653247 (Publication Type: Journal Article)

Chemical References

• Azepines
• Indicators and Reagents
• Platelet Activating Factor
• Triazines
• Triazoles
• WEB 2086
• Thromboxane B2
• Histamine

Topics

• Anaphylaxis (physiopathology)
• Animals
• Azepines (pharmacology)
• Female
• Guinea Pigs
• Histamine (pharmacology)
• In Vitro Techniques
• Indicators and Reagents
• Leukopenia (chemically induced)
• Male
• Passive Cutaneous Anaphylaxis (drug effects)
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Radioimmunoassay
• Respiratory System (drug effects, physiopathology)
• Spectrometry, Fluorescence
• Thrombocytopenia (chemically induced)
• Thromboxane B2 (metabolism)
• Triazines (pharmacology)
• Triazoles