Effects of
thromboxane A2 (TXA2) synthase inhibitors (
CV-4151 and
ozagrel) on
cerebral thrombosis and cerebral damage were examined in a rat middle cerebral artery (MCA)
thrombosis model and their potencies were compared with the conventional
antithrombotic agents,
aspirin and
ticlopidine.
CV-4151 significantly inhibited photochemically induced MCA
thrombosis by oral (1 and 10 mg/kg) and intravenous (1 mg/kg) administration.
Ozagrel (10 mg/kg, p.o.) also inhibited it. The potency of
CV-4151 was about 10 times stronger than that of
ozagrel, being comparable with the inhibition of blood TXA2 generation.
Aspirin (100 mg/kg, p.o.) and
ticlopidine (300 mg/kg, p.o.) showed an inhibitory tendency on MCA
thrombosis. Twenty-four h after photochemical stimulation,
cerebral edema and
cerebral infarction were observed, and the
lactate content in the brain increased.
CV-4151 and
ozagrel prevented this
edema, and the antiedema effects of the drugs were correlated with the antithrombotic effect on thrombotic MCA occlusion.
CV-4151 (10 mg/kg, p.o.), furthermore, significantly reduced the
infarct size and inhibited the increase in
lactate content. These results indicate that TXA2 synthase inhibitors inhibit cerebral damage by inhibition of MCA occlusion with
thrombosis, probably resulting from the inhibition of TXA2 generation, and their effects are superior to those of
aspirin and
ticlopidine. TXA2 might play an important role in cerebral damage in the MCA
thrombosis model.
CV-4151 might be a useful
drug for the treatment of
cerebral thrombosis and for the prevention of
cerebral infarction.