2-3-dinor-6-ketoprostaglandin-f1alpha has been researched along with pirmagrel* in 3 studies
1 trial(s) available for 2-3-dinor-6-ketoprostaglandin-f1alpha and pirmagrel
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Increased thromboxane biosynthesis in a human preparation of platelet activation: biochemical and functional consequences of selective inhibition of thromboxane synthase.
Although thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane A2 might be appropriately assessed. Patients with severe peripheral vascular disease were selected on the basis of elevated plasma beta-thromboglobulin and circulating platelet aggregates and compared with healthy, age-matched control subjects. In addition to the platelet indexes, their bleeding time was shorter and excretion of 2,3-dinor-thromboxane B2, a noninvasive index of thromboxane formation in vivo, and 2,3-dinor-6-keto-prostaglandin F 1 alpha, the major urinary metabolite of prostacyclin, was markedly increased. A selective inhibitor of thromboxane synthase, imidazo (1,5-2) pyridine-5-hexanoic acid, was administered to these patients under randomized, double-blind, controlled conditions. Platelet aggregation ex vivo, the circulating platelet aggregate ratio, and the bleeding time were all unaltered, despite almost maximal inhibition of platelet thromboxane formation 1 hr after dosing. By contrast, pronounced inhibition of aggregation was observed when platelet cyclooxygenase was inhibited by aspirin. During long-term dosing with the synthetic inhibitor, inhibition of thromboxane biosynthesis was incomplete, which would permit continued thromboxane-dependent platelet aggregation to occur. However, the failure of enzyme blockade to influence platelet function at the time of maximal drug action, despite efficient inhibition of serum thromboxane B2, suggests that accumulation of proaggregatory endoperoxides is also likely to have contributed to the persistence of platelet activation. We have characterized a human preparation in which platelet activation coexists with increased thromboxane biosynthesis. In this setting, platelet activation persists despite long-term administration of a thromboxane synthase inhibitor in a dosing regimen representative of that employed in clinical trials. Prolongation of drug action and combination with antagonists of the shared endoperoxide/thromboxane A2 receptor may be necessary to assess the potential of selective inhibition of thromboxane synthase as a therapeutic strategy in man. Topics: 6-Ketoprostaglandin F1 alpha; Aged; Arteriosclerosis; beta-Thromboglobulin; Epoprostenol; Female; Humans; Imidazoles; Male; Middle Aged; Platelet Aggregation; Platelet Factor 4; Pyridines; Thromboxane B2; Thromboxane-A Synthase | 1986 |
2 other study(ies) available for 2-3-dinor-6-ketoprostaglandin-f1alpha and pirmagrel
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Thromboxane synthase inhibition: "endoperoxide shunt phenomenon" does not occur in healthy humans in vivo.
The effects of the thromboxane synthase inhibitor CGS13080 on the in vivo synthesis of thromboxane and prostacyclin were determined in six healthy volunteers. Two different doses (0.08 and 0.25 mg/kg x h) were infused for six hours under strictly controlled conditions and 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha were measured in urine using gaschromatography--mass spectrometry. The in vivo synthesis of thromboxane was inhibited by 80-75% while there was no effect on the in vivo prostacyclin synthesis. Topics: 6-Ketoprostaglandin F1 alpha; Adult; Epoprostenol; Humans; Imidazoles; Male; Pyridines; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes | 1990 |
Comparison of the effects of selective inhibition of thromboxane synthase with those of inhibition of the cyclooxygenase enzyme in man.
Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Imidazoles; Male; Oxidoreductases; Pyridines; Thromboxane-A Synthase; Time Factors | 1984 |