Inihibition of human platelet aggregation by dipyridamole and two related compounds and its modification by acid glycoproteins of human plasma.

The inhibitory effect of dipyridamole (RA 8) and its two derivatives (RA 233 andSH 869) on platelet aggregation in platelet-rich plasma (PRP) AND IN SUSPENSIONSOF WASHED PLATELETS WAS EVALUATED USING 3 AGGRESSING STIMULI: ADP, thrombin, and collagen. Mean effective dose (ED'30) of RA 8 causing 50 percent inhibition of plateletaggregation of washed human platelets by ADP, collagen, or thrombin varied from 1.2 x 10'-7 to 1.8 x 10'-7M. On the other hand, RA 8 caused little inhibition aggregation in human PRP. RA 233 and SH 869 produced similiar degrees of inhibition ofplatelet aggregation in human PRP and in suspensions of washed human platelets.Platelet-poor plasma, fraction VI-acid glycoproteins, or purified alpha'1-acid glycoprotein complex was isolated by means of Sephadex G-25 gel filtration. It is postulated that the formation of this complex leads to the blocking of the capacity of RA 8to inhibit platelet aggragation. RA 233 and SH 869 had little capacity to form complexes with acid glycoproteins of human plasma. This may explain the effectiveness of these compounds in inhibiting platelet aggregation in PRP.