Citric Acid → Cariporide

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

Male Wistar rats (350-450 g) were anesthetized with sodium pentobarbital (50 mg/kg, i.p.). Using a disposable syringe pre-filled with 1.5 ml of 3.8% citric acid solution, 8.5 ml of blood was collected from the abdominal aorta. The blood was centrifuged at 3000 rpm for 5 seconds to obtain platelet rich plasma (PRP). The number of platelets in the PRP was counted by an automatic hemocytometer (Sysmex 2500, TOA Medical Electronics). The PRP was diluted with physiological saline to make the concentration of 40×104 platelets per 1 μl. A platelet aggregometer (Hematoracer, Niko Bioscience) was used for measurement of the platelet swelling. 200 μl of the PRP was poured into a cuvette and 600 μl of sodium propionate solution (Na propionate 135, glucose 10, Hepes 20, CaCl2 1, MgCl2 1; Units: mM; pH6.7) was added while stirring at 37° C. The change in the light transmittance of PRP which was an indicator of the platelet swelling was recorded on a plotter. The test compound was added 3 minutes before addition of the sodium propionate solution. The test compounds were dissolved in dimethylsulfoxide (DMSO). The final concentration of DMSO was adjusted to 1%. The values obtained 1 minute after addition of the sodium propionate solution were subjected to analysis. The rate of inhibition of the test compounds on the increase of the light transmittance was calculated designating the difference obtained between the treatments with 1% DMSO and HOE-642 (10−5M), which is represented by the following formula and a known Na—H exchange inhibitor, as 100%. results are shown as percentage inhibition in Table 1. From these results, it is clear that the compound of the present invention inhibit Na—H exchange.

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