抄録
The effect of dipyridamole dreivatives (RA 233 and VK 744) on platelet function was studied.
A. In vitro studies:
The tests were carried out after incubation of citrated PRP, PPP or whole blood prepared from healthy donors with the inhibitors for 10 min. at the room temperature. Concentrations of both drugs up to 1×10-3 M had no effect on coagulation and fibrinolysis.
Platelet adhesiveness in citrated whole blood according to the glass bead filter method was inhibited by RA 233 at 5×10-5 M and by VK 744 at 2.5×10-5 M. And platelet adhesiveness to glass beads according to Morris was also inhibited by both drugs at 2.5×10-5 M. The availability of platelet factor 3 according to the kaolin clotting time method was inhibited by RA 233 at 2.5×10-5 M and by VK 744 at 1×10-5 M. Prothrombin consumption was likewise inhibited at 1×10-4 M. The release of platelet factor 4 induced by ADP and collagen aggregation was inhibited by RA 233 and VK 744 at 5×10-5 M. Plasma clot retraction was inhibited by RA 233 at 1×10-3 M but not by VK 744 at the same concentration. There were no changes in all parameters of the TEG in citrated whole blood with the exception that the k-time was significantly sheortend at 1×10-3 M (p<0.001).
B. In vivo studies in the rabbit.:
When a single dose of ADP (1.0 ml of 10-3 M) was infused into rabbits, weighing 2.0-2.5 kg, it produced a sudden fall in the circulating platelet count, which was reached ca. 20 sec. after beginning the infusion of ADP with a maximum, ca. 25% of the pretreatment level, and rapidly followed by a return to pretreatment levels. An intravenous administration of a dose of 10 mg/kg RA 233 and VK 744 one minute prior to infusion of ADP (1.0 ml of 10-3 M) had no or little inhibitory effect on a rapid fall in the platelet count.
On the other hand, platelet adhesiveness to the glass bead filter according to Hellem II method was performed at intervals for 8 hours with native whole blood collected by the technique of Rodriguez- Erdmann. An intravenous administration of a dose of 10 mg/kg VK 744 had no effect on platelet adhesiveness in the rabbit.
RA 233 and VK 744 powerfully inhibited human platelet function in vitro, whereas both drugs had no effect on platelet function in the rabbit.
