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Differential Inhibitory Effects of Isosorbide Dinitrate and its Mononitrate Metabolites on Platelet Aggregation and Thromboxane Formation

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Abstract

The effects of isosorbide dinitrate (ISDN) and its 2- and 5-mononitrate metabolites (2-ISMN and 5-ISMN) against platelet aggregation and thromboxane release were investigated by analysis of platelet aggregation curves. ISDN, 2-ISMN and 5-ISMN (isosorbide nitrates, ISN) inhibited both ADP- and epinephrine (EPI)-induced platelet aggregation. ISN affected specifically the extent of ADP-induced aggregation and the velocity of EPI-induced effects. 2-ISMN was more potent against platelet aggregation compared to ISDN and 5-ISMN. The isosorbide nitrates were poor inhibitors of both arachidonic acid-induced aggregation and platelet TxB2 release. The differential inhibition by the three isosorbide nitrates of endogenous TxB2 release during ADP-induced aggregation further indicates that 2-ISMN is a significantly more potent platelet inhibitor than either ISDN or 5-ISMN. These studies suggest a role of the metabolites in modulating the pharmacological effects of ISDN on platelet activity.

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Authors and Affiliations

  1. Département de Pharmacologie Cellulaire, Inserm Sc 16, Faculté de Pharmacie, Marseille

    Pierre H. Rolland

  2. Département de Pharmacologie Cellulaire, Inserm Sc 16, Faculté de Pharmacie, F-13385, Marseille Cedex 5, France

    Pierre H. Rolland

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  1. Pierre H. Rolland
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  2. José Sampol
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  3. Bruno Lacarelle
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  4. Dominique Arnoux
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  5. François Leca
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  6. Elizabeth Gueydon
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  7. Jean-Paul Cano
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Rolland, P.H., Sampol, J., Lacarelle, B. et al. Differential Inhibitory Effects of Isosorbide Dinitrate and its Mononitrate Metabolites on Platelet Aggregation and Thromboxane Formation. Pharm Res 2, 87–90 (1985). https://doi.org/10.1023/A:1016346913143

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