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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 316 (1981), S. 252-255 
    ISSN: 1432-1912
    Schlagwort(e): Carbacyclin-Derivative ; Prostacyclin ; ZK 36 374 ; Vessel tone ; Platelet aggregation ; Platelet disaggregation ex vivo ; Blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The vascular and antiplatelet activities of a new, chemically stable carbacyclin derivative (ZK 36 374) were investigated and compared to PGI2. ZK 36 374 dose-dependently relaxed bovine coronary artery strips in vitro but was without direct effects on strips of bovine coronary veins which were contracted by PGI2. ZK 36 374 dose-dependently inhibited the ADP-, thrombin- and collagen-induced platelet aggregation in human platelet-rich plasma and disperded preformed platelet aggregates in whole blood of cats ex vivo. The IC50 was 0.2–1.1 (antigaggregation) and 13 (disaggregation) nM, respectively, and in the same range as PGI2. The maximum antiplatelet dose of ZK 36 374 (resolution of platelet aggregates) in anaesthetized cats in vivo was 0.45 nmoles/kg x min, and could be increased up to 3 nmoles/kg x min, i.e. 6–7-fold without significant changes in arterial blood pressure and heart rate. This indicates an appreciable dissociation between antiplatelet and blood pressure-lowering activities of this compound, at least in this model. It is concluded that ZK 36 374 is the first, chemically stable prostacyclin-mimetic agent that is equipotent to PGI2 in vitro and might be superior to PGI2 in vivo because of a reduced blood pressure-lowering activity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Journal of molecular medicine 64 (1986), S. 545-551 
    ISSN: 1432-1440
    Schlagwort(e): Iloprost ; Antiplatelet actions ; Blood pressure ; Regional perfusion ; Peripheral arterial obliterative disease (PAOD) ; Dose-response study ; Controlled trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The dose-dependent inhibition of platelet aggregation by the chemically stable, prostacyclin-mimetic, iloprost, was studied in patients suffering from stage II–III peripheral arterial obliterative disease (PAOD). The study was designed as a randomized placebo-controlled cross-over trial. Iloprost was administered i.v. to six patients at doses of 0.5, 1.0, 2.0 or 3.0 ng/kg×min for 4 h, with an interval of 2–3 days between the infusions. During iloprost infusion, systolic and diastolic arterial blood pressure, heart rate and blood flow in the affected limb remained unchanged. In contrast, there was a considerable, dose-dependent inhibition of ADP- and thrombin-induced platelet aggregation and secretion ex vivo at doses of 0.5–2.0 ng/kg×min iloprost, indicating that iloprost reduced platelet stimulation by 50%–70%. The antiplatelet action of iloprost remained unchanged during infusion but ceased with 2 h after administration had ended. The agent was tolerated by the patients without unacceptable side-effects at doses up to 2 ng/kg × min. It is concluded that iloprost administered i.v. at doses of 1–2 ng/kg×min in patients with stage II–III PAOD does not involve haemodynamic side-effects and might be considered an effective antiplatelet agent.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 43 (1992), S. 629-633 
    ISSN: 1432-1041
    Schlagwort(e): Molsidomine, SIN-I, Neutrophil leucocytes ; Aglucuronidase, superoxide anions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The nitrovasodilator and nitric oxide donor molsidomine and its metabolite SIN-I dilate vascular smooth muscle and inhibit platelet activation by increasing intracellular concentrations of cyclic GMP We have therefore studied the effects of molsidomine and SIN-I on isolated human polymorphonuclear leucocytes (PMN)in vitro andex vivo. In vitro molsidomine dose-dependently reducedβ-glucuronidase release and the generation of superoxide anions from non-activated and from FMLP- or PAF-stimulated human PMNs. SIN-1 was equally effective in reducing (β-glucuronidase release and totally inhibited oxygen radical generation at a concentration of 580 μmol · l−1. In a double-blind, placebo-controlled, randomized trial we also studiedβ-glucuronidase release and the generation of superoxide anions from isolated PMNs. Blood was drawn from 12 healthy volunteers before and 3 h after oral molsidomine (16 mg) or placebo. There was no statistically significant difference inβ-glucuronidase release and superoxide anion formation when the PMNs were isolated before or after molsidomine or placebo. This was the case for non-activated, as well as FMLP- or PAF-stimulated PMNs. Thus, the nitric oxide donors molsidomine and its metabolite SIN-I caused a dose-dependent inhibition of PMN functionsin vitro, but no significant inhibition when the PMNs were isolated after oral molsidomine.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1432-1440
    Schlagwort(e): Nisoldipine ; Thromboxane B2 ; 6-Oxo-prostaglandin F1α ; Platelet aggregation ; Blood pressure ; Placebo-controlled study ; Human volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The influence of the calcium antagonist nisoldipine on collagen-induced platelet aggregation and platelet thromboxane formation was studied ex vivo in healthy male volunteers in a double-blind, placebo-controlled crossover design. Measurements of general haemodynamics, immunoreactive 6-oxo-prostaglandin F1α and thromboxane B2 ex vivo and collagen-induced (0.6 and 2.5 µg/ml) platelet aggregation were performed immediately before (time 0), 0.5 h, 1 h and 2 h after ingestion of 10 mg nisoldipine or an identical placebo tablet. Compared with the control response at time 0, administration of nisoldipine resulted in a significant inhibition of both low-collagen-induced platelet aggregation and formation of immunoreactive thromboxane B2 at time 0.5 h. There were no changes in heart rate or systolic blood pressure but a significant decrease in diastolic blood pressure by nisoldipine at 1 h. No such change was obtained with placebo and there were also no alterations with nisoldipine in platelet aggregation and thromboxane formation after stimulation by high-dose collagen at this or any other time of the study. The data demonstrate a platelet-in-hibitory potential of nisoldipine in healthy men which is probably related to an increased resistance of the platelet membrane against foreign stimuli.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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