Antivasoconstrictor and Antiaggregatory Activities of Picotamide Unrelated to Thromboxane A2 Antagonism

Roberta Vezza; Domenico Spina; Ronald J Tallarida; Malevika Nathan; Clive P Page; Paolo Gresele

doi:10.1055/s-0038-1665416

Thrombosis and Haemostasis, Table of Contents

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

¹The Sackler Institute of Pulmonary Pharmacology, Department of Respiratory Medicine, King's College School of Medicine and Dentistry, London, UK;

,

Ronald J Tallarida

²Department of Pharmacology, Temple University, Philadelphia, USA

,

Malevika Nathan

The Institute of Internal and Vascular Medicine, University of Perugia, Perugia, Italy;

,

Clive P Page

¹The 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

Abstract

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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.

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References

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