抄録
The effect of dipyridamole derivatives (RA 233 and VK 744) on human platelet aggregation in vitro was studied. Blood was collected from healthy volunteers who had no drugs for at least one week. Platelet aggregation in citrated platelet rich plasma (PRP) was studied by the turbidometric method of Born using aggregometer (Bryston, Model AG-2) and continuous recording of changes in optical transmission. 0.9 ml of PRP was pre-incubated at the room temperature for 10 min., transferred to the instrument and stirred at 1,100 rpm before adding 0.05 ml or 0.1 ml of aggregating agent. RA 233 and VK 744 were tested in 4 concentrations between 1×10-5 M and 1×10-4 M. RA 233 and VK 744 inhibited ADP-, collagen-, adrenalin-, thrombin- and calcium-induced platelet aggregation.
ADP -induced platelet aggregation (final concentration: 5×10-6 M) was inhibited by RA 233 at 2.5×10-5 M (t-test: p<0.05) and by VK 744 at 5×10-5 M (p<0.02). Collagen-induced platelet aggregation was likewise inhibited by RA 233 at 2.0×10-5 M (p<0.02) and by VK 744 at 5×10-5 M (p<0.01). RA 233 and VK 744 caused active disaggregation when added during ADP and collagen aggregation.
RA 233 and VK 744 inhibited both first and second phase of adrenaline-induced aggregation. At the same concentration RA 233 caused greater inhibition than VK 744, and both drugs greater than dipyridamole (RA 8) and adenosine. RA 233 and VK 744 (dipyridamole derivatives) proved to be very powerful inhibitors of human platelet aggregation in vitro.
