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 pro staglandin pathway through an inhibition of thromboxane A(2) (TXA(2)) synthesis and a competitive antagonism of platelet TXA, receptors. In the present study, we investigated the in vitro, effect of this drug o n human platelet aggregation induced by different agents (adenosine 5' -diphosphate [ADP], collagen, Na arachidonate) both in platelet-rich p lasma (PRP; Born's method) and whole blood (WB; impedance method). For each aggregating agent, ED50 value (agonist concentration necessary t o induce a maximal aggregation of 50%) was determined in control sampl es and following addition of different picotamide concentrations on th e basis of dose-response curves. Picotamide decreased the response to each aggregating agent in both WE and PRP samples. In WB, 25 mu M pico tamide was able to induce a highly significant enhancement of ED50 val ues for ADP (from 6.6+/-1 mu M to 12.7+/-1.7 mu M, p<0.01), Na arachid onate (from 740+/-240 mu M to 1,080+/-280 mu M, p<0,01) and collagen ( from 2.4+/-0.3 mu g/ml to 3.8+/-0.15 mu g/ml, p<0.01). In PRP, the sam e picotamide concentration significantly enhanced ED50 for each aggreg ating agent (from 2.0+/-0.1 mu M to 3.1+/-0.3 mu M for ADP, p<0.01; fr om 960+/-80 mu M to 1,850+/-260 mu M for Na arachidonate, p<0.001; fro m 3.0+/-0.3 mu g/ml to 5.0+/-0.8 mu g/ml for collagen, p<0.01). Presen t results show that picotamide effect on platelet response is present also in WB. Data might support the use of picotamide as antiaggregatin g agent in vascular diseases.