Disease relevance of RP 59227

• Taken together, these data demonstrate that RP 59227 effectively reduces myocardial infarct size and reduces the incidence of ischemia and reperfusion-induced arrhythmias in barbital-anesthetized dogs, and support the concept that PAF plays an important role in the pathogenesis of acute myocardial infarction [1].
• Effect of the platelet-activating factor antagonist RP 59227 (Tulopafant) on myocardial ischemia/reperfusion injury and neutrophil function [1].
• In contrast, the number of dogs which developed ventricular fibrillation during occlusion and reperfusion was significantly less in RP 59227-treated dogs (8 of 11 in the control group vs. 3 of 12 in the RP 59227-treated group, p < 0.05) [1].
• Histological examination revealed marked diminution of both interstitial hemorrhage and deposition of platelet and granulocytes in capillaries of cardiac xenografts when recipient animals were pretreated with tulopafant [2].

High impact information on RP 59227

• Characterization of the antagonist activity of the PAF antagonists RP 59227 and WEB 2086 on elicited guinea pig peritoneal macrophages. Evidence for variable affinities and kinetics [3].
• The apparent noncompetitive effects of RP 59227 were not due to undisplaceable binding to PAF receptors because washing of macrophages exposed to RP 59227 allowed the recovery of PAF luminescence and PAF binding [4].
• The platelet activating factor receptor antagonist, RP 59227, blocks platelet activating factor receptors mediating liberation of reactive oxygen species in guinea pig macrophages and human polymorphonuclear leukocytes [4].
• 1. The potency of platelet activating factor (PAF) as a pro-aggregatory agent and of RP 59227, a selective antagonist of PAF-induced platelet aggregation, was determined in several types of rabbit platelet preparations [5].
• Influence of plasma protein content and platelet number on the potency of PAF and its antagonist RP 59227 in rabbit platelet preparations [5].

Biological context of RP 59227

• The addition of PAF to ex vivo serum was less effective in inducing chemotaxis to eosinophils following RP-59227 (p < 0.05) [6].
• In this study, we provide the first known evidence of the efficacy of the PAF receptor antagonist, tulopafant, in improvement in graft function and histology of discordant cardiac xenografts [2].

Anatomical context of RP 59227

• Myocardial infarct size expressed as a percent of the area at risk (control, 39.0 +/- 5.0; RP 59227, 24.8 +/- 3.4%) or as a percent of the left ventricle (control, 15.3 +/- 1.9; RP 59227, 9.0 +/- 1.3%) was significantly smaller in the RP 59227-treated group [1].
• The effect of the platelet activating factor antagonist RP 59227 (Tulopafant) on myocardial infarct size was compared to that of a vehicle-treated control group in barbital-anesthetized dogs subjected to 90 min of left circumflex coronary artery occlusion and 5 h of reperfusion [1].
• Northern blot analysis revealed that the expression of TNF-alpha mRNA induced by lipopolysaccharide (LPS) in Kupffer cells was partially abrogated by WEB 2170 or RP 59227 [7].

Gene context of RP 59227

• Tulopafant, a PAF receptor antagonist, increases capillary patency and prolongs survival in discordant cardiac xenotransplants [2].
• There was a significant inhibitory effect (p < 0.05) in peak ECA and NCA in blood after RP-59227 [6].

Analytical, diagnostic and therapeutic context of RP 59227

• Platelet activating factor antagonist RP-59227 reduces vascular injury in discordant cardiac xenograft rejection [8].
• Design: We determined the safety and efficacy of a 240 mg oral dose of RP-59227 in attenuating the early and late phase antigen challenge in eight asthmatics, using a double-blind, placebo-controlled, crossover design [6].

References