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Thromb Haemost 1989; 61(03): 479-484
DOI: 10.1055/s-0038-1646618
Original Article
Schattauer GmbH Stuttgart

Characterization of N,N’-bis(3-Picolyl)-4-Methoxy-Isophtalamide (Picotamide) as a Dual Thromboxane Synthase Inhibitor/Thromboxane A2 Receptor Antagonist in Human Platelets

P Gresele
1   The Centre for Thrombosis and Vascular Research, University of Leuven, Leuven, Belgium
2   The Istituto di Semeiotica Medica, University of Perugia, Perugia, Italy
,
H Deckmyn
1   The Centre for Thrombosis and Vascular Research, University of Leuven, Leuven, Belgium
,
J Arnout
1   The Centre for Thrombosis and Vascular Research, University of Leuven, Leuven, Belgium
,
G G Nenci
2   The Istituto di Semeiotica Medica, University of Perugia, Perugia, Italy
,
J Vermylen
1   The Centre for Thrombosis and Vascular Research, University of Leuven, Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Received 26 May 1988

Accepted after revision 02 February 1989

Publication Date:
24 July 2018 (online)

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Summary

Picotamide (G137 or N,N’-bis[3-picolyl]-4-methoxy-iso- phtalamide), a drug which has shown platelet inhibitory effects in vitro and ex vivo, was investigated for its mechanism of action on human platelets in vitro. This compound suppresses the aggregation of human platelets induced by arachidonic acid (IC50: 1.8 × 1(T5 M), low-dose collagen (IC50: 3.5 × 10-4 M), U46619 (IC50: 1.4 × 10-4 M) and by authentic TxA2 (IC50: 1 × 10-4 M), without affecting the aggregation induced by A23187 or primary aggregation by ADP. Picotamide inhibits dose-dependently TxA2 synthesis by platelets (IC50: 1.5 × 10-4 M) and enhances the formation of PGE2. Picotamide-treated platelets also favour the formation of PGI2 by aspirinated endothelial cells; in addition, the drug appears to exert a direct stimulatory effect on PGI2- synthesis, at least at high concentrations. Finally, in platelet-rich plasma stimulated with arachidonic acid, picotamide increases intraplatelet cAMP while no effects on cAMP are detected in unstimulated platelets.

In conclusion, picotamide is a dual thromboxane-synthase inhibitor/thromboxane-receptor antagonist in human platelets and introduces a new class of agents potentially useful in antithrombotic therapy.

Keywords

Antithrombotics - cAMP - Platelet inhibition - Prostacyclin
 

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