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F-0401 is a newly synthesized dihydropyridine derivative with both antagonistic activity on platelet-activating factor (PAF) and inhibitory action on thromboxane A2(TXA2) synthetase activity. In the present study, we examined the effects of F-0401 on platelet aggregations in vitro and ex vivo in rabbits. F-0401 prevented PAF-, arachidonic acid (AA)- and collagen-induced platelet aggregations in vitro, but did not prevent the aggregation by ADP. The inhibitory effect of F-0401 on the aggregation by PAF (IC50 value: 3.4 x 10(-6) M) or by the threshold amount of AA (IC50 value: 4.3 x 10(-6) M) had the same potency as that of CV-3988 (a PAF antagonist) and ozagrel a (TXA2 synthetase inhibitor). Ex vivo studies also revealed that the anti-aggregatory effect occurred 1 h after the treatment of F-0401 (&gt; 10 mg/kg, p.o.) and this effect had a tendency to last for 6 h. Nicardipine prevented the platelet aggregation only by PAF (IC50 value: 6.6 x 10(-5) M) in vitro. However, the preventive effect was not seen ex vivo. On the other hand, neither nifedipine nor flunarizine showed any effect on the stimulant-induced platelet aggregation in rabbits. These results suggest that F-0401 has anti-aggregatory action, which is attributable to both PAF antagonistic action and TXA2 synthetase inhibition in vitro and ex vivo.

Pharmacological Profile of F-0401, a Novel Dihydropyridine Derivative. III. The Anti-Aggregatory Action of F-0401 on Rabbit Platelets