Platelet anti-aggregant and rheological properties of piracetam. A pharmacodynamic study in normal subjects.
The random administration of four different single oral doses of piracetam (Nootropil, CAS 7491-74-9)--1.6 g, 3.2 g, 4.8 g and 9.6 g--at fixed intervals of 2 weeks to 5 healthy subjects has confirmed and explicited its platelet anti-aggregant and rheological properties after doses of 4.8 g and 9.6 g. The effect on platelet aggregation occurs through inhibition of thromboxane synthetase or anti-thromboxane A2 activity together with a reduction in the plasma level of von Willebrand's factor (F.VIIIR:vW). The rheological effect is related to the action of piracetam on cell membrane deformability (red cells, white cells and platelets) and to its simultaneous effect in reducing by 30-40% plasma levels of fibrinogen and von Willebrand's factor. In addition, it exerts a direct stimulant effect on prostacyclin synthesis in healthy endothelium. These effects are greatest between 1 and 4 h after dosage, and then diminish progressively to disappear between 8 and 12 h after administration. This explains the need to divide the total daily dose into 3 intakes at 8-hourly intervals. This study confirms the presence of four sites of action of piracetam: the vessel wall, platelets, plasma and cell membranes (RBC, WBC), which provide the basis for the potentially important antithrombotic activity of piracetam.
Moriau
M
M
Department of Internal Medicine, University of Louvain (UCL), St.-Luc University Clinics, Brussels, Belgium.
Crasborn
L
L
Lavenne-Pardonge
E
E
von Frenckell
R
R
Col-Debeys
C
C
D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005340:Fibrinogen / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D008297:Male; D010889:Piracetam / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count / Q000187:drug effects; D010978:Platelet Factor 4 / Q000378:metabolism; D012016:Reference Values; D013929:Thromboxane B2 / Q000378:metabolism
D005344:Fibrinopeptide A; D010978:Platelet Factor 4; D013929:Thromboxane B2; D000990:Antithrombin III; D005340:Fibrinogen; D010889:Piracetam