In vitro effects of picotamide on human platelet aggregation, the release reaction and thromboxane B2 production.
We studied the in vitro effects of picotamide (N,N' bis 3 picolyl-4-methoxy-isophthalamide) on human platelet aggregation, the release reaction and the production of thromboxane B2 (TxB2) induced by several platelet agonists. The effects of picotamide were compared to those of acetylsalicylic acid (ASA). Picotamide (0.5 mmol/l) inhibited platelet aggregation, the release of ATP and TxB2 production induced by ADP, arachidonic acid (AA), collagen or the prostaglandin endoperoxide (PE) analogue U46619. ASA (0.5 mmol/l) did not affect platelet aggregation and the release of ATP induced by U46619. Picotamide and ASA inhibited the AA-induced platelet TxB2 production both under stirring and non-stirring conditions, whereas the pure thromboxane A2 receptor antagonist BM13177 (0.5 mmol/l) was inhibitory only under stirring conditions. Since under non-stirring conditions platelet aggregation does not occur, picotamide directly inhibits TxB2 production, whereas BM13177 inhibits the potentiation of TxB2 production due to TxA2/PE-dependent platelet aggregation. Malondialdehyde (MDA) production by unstirred platelets stimulated with AA was not significantly inhibited by picotamide. In conclusion, picotamide inhibits the TxA2/PE-dependent platelet responses to agonists by a double mechanism: (i), TxA2/PE antagonism; (ii) inhibition of thromboxane synthase.
A. Bianchi Bonomi Hemophilia and Thrombosis Center, I.R.C.C.S. Maggiore Hospital, Italy.
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Cattaneo
P M
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Tenconi
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Lecchi
P M
PM
Mannucci
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010795:Phthalic Acids / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*
D010795:Phthalic Acids; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D016718:Arachidonic Acid; D008315:Malondialdehyde; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C011581:picotamide; C040624:sulotroban; D000255:Adenosine Triphosphate; D003094:Collagen; D001241:Aspirin