Thromb Haemost 1997; 78(05): 1385-1391
DOI: 10.1055/s-0038-1665416
Review Article
Schattauer GmbH Stuttgart

Antivasoconstrictor and Antiaggregatory Activities of Picotamide Unrelated to Thromboxane A2 Antagonism

Roberta Vezza
The Institute of Internal and Vascular Medicine, University of Perugia, Perugia, Italy;
,
Domenico Spina
1   The Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine, King's College School of Medicine and Dentistry, London, UK;
,
Ronald J Tallarida
2   Department of Pharmacology, Temple University, Philadelphia, USA
,
Malevika Nathan
The Institute of Internal and Vascular Medicine, University of Perugia, Perugia, Italy;
,
Clive P Page
1   The Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine, King's College School of Medicine and Dentistry, London, UK;
,
Paolo Gresele
The Institute of Internal and Vascular Medicine, University of Perugia, Perugia, Italy;
› Author Affiliations
Further Information

Publication History

Received 16 1996

Accepted after resubmission 09 July 1997

Publication Date:
12 July 2018 (online)

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Summary

Picotamide is a dual thromboxane (Tx) A2 receptor antagonist/Tx synthase inhibitor although some observations suggest an anti-vasoconstrictor effect independent of TxA2 inhibition/antagonism. The aim of our study was to assess whether picotamide antagonises vascular contractions induced by different vasoactive substances in vitro. Picotamide inhibited competitively the contraction of rabbit aortic rings induced by the TxA2 mimetic U46619 (pA2 = 3.59) but also the contractions induced by phenylephrine (pA2 = 3.93) and serotonin (5-HT) (pA2 = 5.81) although in a not competitive way. Picotamide did not inhibit potassium-induced contractions, thus excluding aspecific effects on vascular smooth muscle. Picotamide inhibited 5-HT-induced platelet aggregation in vitro with an IC50 (212 μM) similar to that found when other aggregating stimuli are used, but it did not affect shape change (IC50> 1 mM) suggesting that the effects of picotamide can not be ascribed to 5-HT2-receptor antagonism; in the same experimental conditions neither a Tx-receptor antagonist (BM13.177) nor a dual Tx-receptor antagonist/synthase inhibitor (ridogrel) affected 5-HT-induced platelet responses.

Our studies demonstrate that picotamide exerts antivasoconstrictor and platelet inhibitory effects unrelated to TxA2 antagonism. This activity may contribute to the anti-thrombotic/anti-ischaemic effects of the drug in vivo.