Pharmacological and Toxicological Studies on a New Hypolipidemic Agent ,NlP-200

• Published in: Japanese Journal of Pharmacology Vol. 40; no. suppl; p. 231
• Main Authors: Mitsuaki Sakashita, Nobutomo Tsuruzoe, Morihide Hibi, Iwao Kaneko, Yoshihiro Fujikawa, Ryozo Sakoda, Yasushi Saito
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1986
• ISSN: 0021-5198; 1347-3506

In the previous studies ,we showed that NlP-200,3,5-dimethyl-4,6-diphenyl-tetrahydro-1,3,5-thiadiazine-2-thione, had a potent hypolipidemic effect and increased serum high density lipoprotein-cholesterol(HDL-C) in lipid emulsion-induced and cholesterol-fed hyperlipidemic rats(Abstracts, 17th annual meeting of Japan Atheroscler. Soc., 1985). In the present study,this structurally novel hypolipidemic agent,NlP- 200 was evaluated further by the pharmacological and toxicological study. In the pharmacological studies, the effects of NIP-200 on cholesterol-fed mice and Triton-induced hyperlipidemic rats were investigated in comparison with those of clofibrate(CF). NIP-200(150 mg/kg/day,p.o., 7days) significantly lowered serum total cholesterol(TC) by 34% and liver total lipids(TL) by 34% in cholesterol-fed mice. This hypolipidemic activity was higher than that of CF. Serum HDL-C was not elevated by NIP-200. In Triton-induced hyperlipidemic rats,NIP-200 had no effect on serum TC and triglyceride(TG) ,while CF lowered serum TC and TG by 27% and 25%,respectively. In the toxicological studies,NIP-200 was proved to have a low acute toxicity(LD_50 ; ＞8000mg/kg,p.o., ＞4000mg/kg,i.p.in male mice) and to show no mutagenicity(Ames test).