Effects of the synthetic ether phospholipid KO-286011 on cells and components of rabbit blood

The ether phospholipid KO-286011, which is related to platelet-activating factor (PAF), was examined for PAF-antagonistic action on rabbit platelets both in vitro and ex vivo. It inhibited the aggregation of washed platelets induced by PAF (5 nmol/l) concentration dependently (IC50 = 6.5 X 10(-7) mol/l). After injecting 0.5 mg/kg to rabbits, the ex vivo PAF-mediated aggregation in heparinized platelet-rich plasma was influenced selectively. The inhibition was short and maximal after 5 min. In contrast, hematocrit, counts of peripheral platelets and leukocytes, hemoglobin content, partial thromboplastin time, prothrombin time, and fibrinolytic activity in plasma were not affected. However, the therapeutic range of KO-286011 is limited because of membranolytic activity at higher dosages, leading to hemolysis and drop of circulating platelet counts.