cinnarizine and Thrombosis

Dipfluzine (Dip) is a novel diphenylpiperazine calcium channel blocker first synthesized in China. Effects of Dip on experimental thrombosis and platelet aggregation were studied in vitro and in vivo compared with cinnarizine (Cin). Dip 1 and 2 mg.kg-1 i.v. and incubated in 1-100 mumol.L-1 in vitro inhibited dose- or concentration-dependent rabbit platelet aggregation induced by ADP and by arachidonic acid (AA), respectively. Dip 2.5-10 mg.kg-1 i.v. and 50-100 mg.kg-1 ip inhibited the thrombosis in rats. Dip 10 mg.kg-1 i.v. and 200 mumol.L-1 depressed the in vitro thrombosis. These results suggest that attenuation of disturbed platelet-vessel wall reaction associated with platelet activation and vasoconstriction may be a main factor involved in the antithrombotic action of Dip, and that the effects of Dip were more potent than those of Cin.

Topics: Animals; Carotid Artery Thrombosis; Cinnarizine; Dose-Response Relationship, Drug; Female; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Rats; Rats, Wistar; Thrombosis

Flunarizine in vivo protects against endothelial cell damage induced by intravenous injection of citrate, CaCl2, or lactate in rats. Its effect is optimal at the low oral dose of 0.1 mg/kg, corresponding to the clinically used one. It lasts for at least 8 hours. Edema formation, platelet activation, and venostatic thrombosis subsequent to endothelial cell injury consequently are also inhibited by flunarizine. The compound does not affect platelet function, plasma coagulation or generation of PGI2 by vascular tissue and does not impair normal haemostasis at effective doses. As for its vascular and hemorrheological effects, the protection by flunarizine against endothelial injury may be related to its Ca2+-antagonistic properties.

Topics: Animals; Blood Vessels; Calcium Chloride; Cinnarizine; Endothelium; Female; Flunarizine; Hemostasis; Piperazines; Platelet Aggregation; Rats; Thrombosis