Disease relevance of Taprostene

• Also with treatment starting 1 hour after the onset of endotoxemia CG 4203 in the same doses significantly inhibited the endotoxin-induced lethality [1].
• Our results suggest that inhibition of platelet aggregation, as well as the antiproteolytic and membrane-stabilizing actions, could mediate the beneficial effects of CG-4203 in hemorrhagic shock [2].
• Our results suggest that a combination of membrane stabilizing and anti-proteolytic effects and inhibition of platelet aggregation may mediate the protective effects of CG-4203 in traumatic shock [3].
• The relevance of this activity is discussed with respect to the CG 4203 treatment of occlusive vascular diseases [4].
• CG 4203 infusion marginally attenuated thrombocytopenia and obviously inhibited leukopenia, but did not effect fibrinogen consumption in endotoxemic rats [1].

High impact information on Taprostene

• Salutary effects of the prostacyclin analogue CG 4203 in lethal endotoxemia in rats [1].
• Hemorrhaged rats treated with CG-4203 maintained postreinfusion mean arterial blood pressure (MABP) at significantly higher values than rats receiving only the vehicle (final MABP 101 +/- 3 vs. 75 +/- 5 mm Hg, p less than 0.01) [2].
• Both 25 and 35 ng/kg/min doses of CG 4203 produced approx. 50% inhibition of the ADP-induced platelet aggregation for the entire 5 h administration period [5].
• Traumatized rats treated with CG-4203 exhibited significantly lower plasma activities of the lysosomal hydrolase cathepsin D (p less than 0.05) [3].
• While heparin has no significant effect on the in vitro BT, CG 4203 prolongs it concentration-dependently [6].

Biological context of Taprostene

• However, CG-4203, at concentrations expected during treatment of shock, failed to have an immediate or delayed vasodilator effect in rat aortic rings, and thus vasodilation is not an important aspect of the antishock effects of CG-4203 [2].
• Similarly, CG 4203 (0.21 - 4.64 micrograms X kg-1 X min-1) dose-dependently caused increased water intake which was prevented by previous nephrectomy [7].
• Within a similar dose range CG 4203 dose-dependently inhibited diuresis and saluresis and reduced the urinary sodium/potassium ratio [7].

Anatomical context of Taprostene

• Slight falls in thrombocytes and in some case substantial falls in leukocytes shortly after commencing the dialysis cannot be avoided when administering CG 4203 alone [5].
• In anaesthetized rats, CG 4203 (1.0 microgram X kg-1 X min-1 i.v.) significantly reduced incidence of ventricular fibrillation and increase in plasma CK activity after ligation of the left coronary artery [8].

Associations of Taprostene with other chemical compounds

• Infusion of the prostacyclin analogue CG 4203 (0.464 and 1.0 micrograms.kg-1.min-1 for 6 hours), starting concomitantly with the endotoxin infusion, improved the survival rate to 95 and 100% [1].

Gene context of Taprostene

• Direct urokinase like activation of plasminogen does not occur with CG 4203 [4].
• CG 4203 infused intravenously starting at 1 microgram X kg-1 X min-1 induced both a fall in blood pressure and an increase of plasma renin activity [7].

Analytical, diagnostic and therapeutic context of Taprostene

• Hemodialysis with the stable prostacyclin analogue CG 4203 [9].
• In isolated perfused rat hearts, CG 4203 (4.64 X 10(-9) mol/l) significantly attenuated arrhythmias and loss of left ventricular creatine kinase (CK) activity observed in control hearts after 30 min perfusion with hypoxic and 30 min reperfusion with oxygenated Krebs-Ringer solution [8].

References