Animal experiment:

Mice[1]Male mice, strain ddY, 6 weeks old are used in the assay. The mice are fasted overnight and then Triton WR-1399 (500 mg/kg) is intravenously injected. Immediately and 8 h after the injection, AZ-1366 or clofibrate (both 150 mg/kg, each) are given to the mice orally. The control mice receive the vehicle, 1% aqueous methycellulose. The mice are maintained for 24 h on drinking water only and then the blood is withdrawn from the heart. Rats[1]Male rats, strain Sprague-Dawley, 6 weeks old are used in the assay. A total of 56 rats are randomly assigned to 2 equal groups. One group is fed the CE-2 diet and the other the high fat diet. Each group is further subdivided into 4 equal groups (n=7). The rats in the first subgroup receives the vehicle, 5% aqueous gum arabic solution, orally (1 ml 100 g body weight). The second sub-group receives clofibrate (100 mg/kg daily), and the third and the fourth receive AZ-1355 in daily doses of 50 and 100 mg/kg, respectively. The drug is administered once a day for 4 consecutive weeks. Body weights are monitored daily. There is no difference in weight gains between the treated and corresponding control groups.

AZ-1355 is an effctive lipid-lowering compound, which also inhibits platelet aggregation in vivo and elevates the prostaglandin I2/thromboxane A2 ratio in vitro.

AZ-1355 (50 mg/kg) significantly reduces serum TG and the 100 mg/kg dose results in serum TC and TG reduction in rat. AZ-1355 (100 mg/kg) reduces total liver TC in rats fed CE-2, and the 50 mg/kg dose reduces hepatic TC in rats fed the high fat diet on both bases, and it also reduces the total hepatic TG of the CE-2 fed rats. AZ-1355 (150 mg/kg) reproducibly lowers serum total cholesterol (TC) in the Triton hyperlipidemic mice[1].

[1]. Wada S, et al. The lipid-lowering profile in rodents. AZ-1355, a new dibenzoxazepine derivative. Atherosclerosis. 1981 Nov-Dec;40(3-4):263-71.