Studies on in vitro effect of picotamide on human platelet aggregation in platelet-rich plasma and whole blood.
Picotamide is a new antiaggregating agent influencing the platelet prostaglandin pathway through an inhibition of thromboxane A2 (TXA2) synthesis and a competitive antagonism of platelet TXA2 receptors. In the present study, we investigated the in vitro effect of this drug on human platelet aggregation induced by different agents (adenosine 5'-diphosphate [ADP], collagen, Na arachidonate) both in platelet-rich plasma (PRP; Born's method) and whole blood (WB; impedance method). For each aggregating agent, ED50 value (agonist concentration necessary to induce a maximal aggregation of 50%) was determined in control samples and following addition of different picotamide concentrations on the basis of dose-response curves. Picotamide decreased the response to each aggregating agent in both WB and PRP samples. In WB, 25 microM picotamide was able to induce a highly significant enhancement of ED50 values for ADP (from 6.6 +/- 1 microM to 12.7 +/- 1.7 microM, p < 0.01), Na arachidonate (from 740 +/- 240 microM to 1,080 +/- 280 microM, p < 0.01) and collagen (from 2.4 +/- 0.3 micrograms/ml to 3.8 +/- 0.15 micrograms/ml, p < 0.01). In PRP, the same picotamide concentration significantly enhanced ED50 for each aggregating agent (from 2.0 +/- 0.1 microM to 3.1 +/- 0.3 microM for ADP, p < 0.01; from 960 +/- 80 microM to 1,850 +/- 260 microM for Na arachidonate, p < 0.001; from 3.0 +/- 0.3 microgram/ml to 5.0 +/- 0.8 micrograms/ml for collagen, p < 0.01). Present results show that picotamide effect on platelet response is present also in WB. Data might support the use of picotamide as antiaggregating agent in vascular diseases.
Anfossi
G
G
Department of Clinical and Biological Sciences, University of Turin, Italy.
Parisi
S
S
Russo
I
I
Mularoni
E M
EM
Massucco
P
P
Cavalot
F
F
Mattiello
L
L
Trovati
M
M
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000328:Adult; D000704:Analysis of Variance; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D003094:Collagen / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010795:Phthalic Acids / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D010795:Phthalic Acids; D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C011581:picotamide; D003094:Collagen