Inhibition of the vascular actions of IgG aggregates by BN 52021, a highly specific antagonist of paf-acether.
The effect of BN 52021, a selective antagonist of paf-acether (Braquet GB patent 8, 418, 424 July 19, 1984), was studied in normotensive rats challenged with different doses of paf-acether. Sudden death was observed in animals receiving an i.v. dose of 10 micrograms/kg of paf-acether and this was prevented by prior treatment with BN 52021 (5 mg/kg, i.v.). Animals receiving 2.5 micrograms/kg of paf-acether had a fall of mean arterial pressure of 92.5 +/- 4.7 mmHg which recovered to the prechallenge level 20.5 +/- 0.2 min thereafter. Previous treatment with BN 52021 (5 mg/kg, i.v.) reduced the mean arterial pressure fall to 47 +/- 0.9 mmHg and the time of recovery to 5.7 +/- 1.7 min. The extravasation of 125I-bovine serum albumin under the above conditions was reduced by BN 52021 from 36 +/- 3 to 18 +/- 3%. A lower dose of BN 52021 (1 mg/kg, i.v.) was also effective in reducing later extravasation, but was unable to prevent the extravasation which appears up to 10 min after the injection of paf-acether. To extend these findings to a model of endogenous production of paf-acether, other animals were challenged with soluble aggregates of human IgG (40 mg/kg, i.v.; Iñarrea et al., Immunopharmacology 6:7, 1983).(ABSTRACT TRUNCATED AT 250 WORDS)
D000707:Anaphylaxis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004224:Diterpenes; D046934:Ginkgolides; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007074:Immunoglobulin G; D007783:Lactones; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D004224:Diterpenes; D046934:Ginkgolides; D007074:Immunoglobulin G; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C045856:ginkgolide B