Chinoin-7284 and Chinoin-7384 are chemically stable derivatives of prostacyclin. We compared the hypotensive and antiaggregatory effects of PGI2 and the two analogues using our computerized aggregometric system. The in vivo antiaggregatory activity was measured with a modified filtration pressure technique in anaesthetized beagle dogs: The change in arterial blood pressure was measured simultaneously. The dose-response relationship and the duration of action of prostacyclin and their analogues following bolus administration have been determined. The molar dose of PGI2, CH-7284 and CH-7384 that produced 25 mmHg reduction in filtration pressure were 0.3±0.06 nmol/kg; 7.37±0.94 nmol/kg; 17.19±1.76 nmol/kg respectively (n=6). The molar doses that produced the same decrease in mean arterial pressure were 0.61±0.06 nmol/kg; 15.59±4.73 nmol/kg; 21.05±7.20 nmol/kg respectively (n=6). There were no significant differences between equipotent doses of prostacyclin and its analogues with respect to the duration of antiaggregatory and hypotensive action. The in vivo selectivity ratios (hypotensive potency/antiaggregatory potency) of PGI2, CH-7284 and CH-7384 were 0.49, 0.47 and 0.85 respectively. The results indicate that these two PGI2 analogues have the same character as regards the in vivo duration of actions and in vivo selectivity, as has the parent compound.
|Journal||Biomedica Biochimica Acta|
|Publication status||Published - Jan 1 1988|
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