In vivo inhibition of plasma protein leakage andSalmonella enteritidis—induced mortality in the rat by a specific paf-acether antagonist: BN 52021

Abstract

The effects of BN 52021, a new specific paf-acether receptor antagonist and the total Ginkgo Biloba extract (GBE 761) from which this product was isolated, were studied in the rat on paf-acether-induced permeability and cell number changes and on endotoxin-induced lethality. Their activities were compared to those of cyclooxygenase, 5-lipoxygenase and phospholipase A2 inhibitors. BN 52021 given s.c. or orally exerted a dose-related inhibition of paf-acether deleterious effects as well as of endotoxin lethality whereas the other drugs tested were poorly effective. These results strongly suggest paf-acether involvement in endotoxic and septic shock.

PAF Antagonists as Potential Therapeutic Agents in Cardiac Anaphylaxis and Myocardial Ischemia

“…The cardioprotective effect seems to be due to the specific PAF antagonist property, since the concentration of BN 5202 1 showing antiarrhythmic activity during ischemia is in the same range as that which inhibits carlac anaphylactic symptoms. The role of PAF and its antagonists in Ca2+ metabolism has already been discussed; however, it should be noted that in contrast to calcium channel blockers, exhibiting a PAF antagonist property (26), BN 52021 does not produce a negative inotropic effect on the heart even in high concentrations. Therefore, the antiarrhythmic effect of the PAF antagonist is unlikely to be due to a blocking effect on slow Ca2+ channels.…”

“…PAF is released in shock induced by endotoxin and immune aggregates, and BN 52021 (1,26,29) as well as other PAF antagonists, such as L-652,73 1 (40), kadsurenone (24), CV 3988 (78), and SRI 63072 and 63441 (35), have been found toprevent endotoxininduced hemodynamic changes. The local vasodilator effect of PAF in the region of gastric, mesenteric, and femoral arteries contributes to local tissue damage (23).…”

Biosynthesis pathways of ginkgolides

“…[2] Bilobalide exhibits neuroprotective effects by decreasing the release of excitotoxic amino acids, particularly glutamate and aspartate. [3] Ginkgolides have many pharmacological activities such as acting as specific platelet-activating factor antagonists,[4] selective antagonists of glycine receptors,[5] etc., The commercial ginkgolides are produced merely from G. biloba plants, especially from the ginkgo leaves. But the contents of ginkgolides in the native ginkgo plants are very low.…”

Comparison of the reversed passive Arthus and local Shwartzman reactions of rabbit skin: effects of the long‐acting PAF antagonist UK‐74,505

“…Thus, PAF, injected i.v., reproduces many of the features of clinical or experimental septic shock (Anderson et al , 1991; Qian et al , 1994). PAF antagonists protect against LPS or bacteria‐induced shock in different animal models (Terashita et al , 1983; Etienne et al , 1985; Toyofuku et al , 1986; Casals‐Stenzel, 1987; Chang et al, 1987; Fletcher et al , 1989; Kuipers et al , 1994) and elevated PAF concentrations have been detected in the plasma of sepsis patients (Bussolino et al , 1987). Furthermore, a recent phase II clinical trial indicated improved organ failure statistics in patients treated with a PAF antagonist (Froon et al , 1996).…”