Effects of dilazep (AS-05) on human blood platelet aggregation.

The effects of tetrahydro-1H-1,4-diazepine-1,4 (5H)-dipropanol-3,4,5-trimethoxybenzoate diester (dilazep) on platelet aggregation were studied by aggregometer-technique in vitro, using platelet-rich plasma obtained from healthy subjects. As agents for platelet aggregation, norepinephrine, at a concentration of 10 micrograms/ml, and ADP, at a concentration of 1 microgram/ml, were added. There was some inhibition when compared to controls with 200 micrograms/ml of dilazep, and complete inhibition on both norepinephrine and ADP-induced platelet aggregation with 500 micrograms/ml. The effects of dilazep on platelet aggregation before and after administration (75 mg) in vivo, using platelet-rich plasma obtained from healthy subjects, were studied in accordance with the screen filtration pressure method. In all cases the inhibitory tendency was first seen 30 min after administration. It reached a peak after 60--120 min and tended to return to the initial value after 180 min. The effects of dilazep (150 mg/day for 4 weeks) and verapamil hydrochloride (240 mg/day for 4 weeks) on platelet aggregation in vivo, using plasma obtained from sixteen patients with coronary insufficiency, were determined in each group before and after drug administration. A significant difference in the group receiving dilazep was found at tO = 3.2643 and less than 0.01 in the Student's t-test (two dependent sample cases). In the experiments with verapamil hydrochloride there were no significant differences in the results before and after administration. However, there was a slight tendency towards a decrease of effects two weeks after administration.