Effects of clopidogrel on platelet activation and coagulation of non-anticoagulated rat blood under high shear stress.
Clopidogrel is a new thienopyridine derivative similar to ticlopidine, which inhibits adenosine diphosphate-induced platelet aggregation. The in vitro effects of clopidogrel on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. Clopidogrel significantly inhibited shear-induced platelet activation and coagulation 2 h after administration at doses of 7.5 and 15 mg/kg. Both ticlopidine (200 mg/kg) and aspirin (200 mg/kg) inhibited shear-induced platelet activation, but not coagulation. The peak inhibition of plaetelet activation by clopidogrel occurred 2 h after oral administration, but significant inhibition persisted even after 24 h. These results suggest that clopidogrel could be a more potent antithrombotic agent than ticlopidine or aspirin, and also that ADP plays an important role in shear-induced platelet activation.
Taka
T
T
Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan.
Okano
E
E
Seki
J
J
Yamamoto
J
J
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D000077144:Clopidogrel; D006489:Hemostatic Techniques / Q000295:instrumentation; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin