Interaction of platelets with subendothelium in rats treated with PCA-4230, a new antithrombotic agent. Effect of PCA-4230 on experimental thrombosis.
The effects of a new antithrombotic compound, PCA-4230, versus ticlopidine were investigated using an experimental thrombosis and vascular endothelial injury model in rats. Both PCA-4230 and ticlopidine protected rat arteries from the formation of prominent thrombi and most of microthrombi without modifying the formation of a first platelet monolayer. Neither coagulation parameters nor fibrinolysis were modified by these antithrombotic drugs. Neither PCA-4230 nor ticlopidine affected thromboxane A2 production in rats, whereas unlike PCA-4230, ticlopidine inhibited ex vivo fibrinogen binding to the fibrinogen receptor found on the platelet membrane. In conclusion, PCA-4230 and ticlopidine inhibited thrombus formation in vivo by a platelet-dependent mechanism which may be different for one or the other drug in spite of the fact that the protective effect measured in this thrombosis model is quite similar for either PCA-4230 or ticlopidine. The above-mentioned results clearly show that PCA-4230 is a new potent agent with both antivascular-damaging and antiplatelet activities, and devoid of effects on coagulation and fibrinolytic systems.
Gutiérrez Díaz
J A
JA
Alter, S.A., Departamento de Investigación, Madrid, España.
Tolón
R M
RM
Sunkel
C
C
Priego
J G
JG
Ortega
M P
MP
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism* / Q000648:ultrastructure; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000517:prevention & control; D013929:Thromboxane B2 / Q000032:analysis; D013988:Ticlopidine / Q000494:pharmacology
D004095:Dihydropyridines; D005343:Fibrinolytic Agents; D010980:Platelet Membrane Glycoproteins; C073664:PCA 4230; D013929:Thromboxane B2; D005340:Fibrinogen; D013988:Ticlopidine