Iwakura K, Tamura H, Yamashita Y, Kitayama E, Hamasu Y, Nagasawa H, Watanabe M, Sumi N
Research Laboratories, Nippon Shinyaku Col Ltd., Kyoto, Japan.
J Toxicol Sci. 1995 Dec;20 Suppl 2:325-34. doi: 10.2131/jts.20.supplementii_325.
Montirelin hydrate (NS-3), a new drug for the treatment of disturbance of consciousness, was examined for mutagenicity in the reverse mutation test, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at dose range of 156.25-5,000 micrograms/plate using Salmonella typhimurium strains, TA1535, TA100, TA1537, and TA98, and Escherichia coli WP2uvrA. The drug did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S-9mix). The chromosome aberration test was carried out at dose range of 300-4,800 micrograms/ml using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosomal aberrations were observed with or without metabolic activations. The micronucleus test was conducted in the bone marrow cells of Slc:ddY male mice. Mice were given the drug by a single intraperitoneal administration at doses of 0, 250, 500, 1,000, and 2,000 mg/kg. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that montirelin hydrate has no mutagenic activity in vitro or in vivo.
水合蒙特瑞林（NS - 3）是一种用于治疗意识障碍的新药，在回复突变试验、体外染色体畸变试验和小鼠微核试验中对其致突变性进行了检测。回复突变试验使用鼠伤寒沙门氏菌菌株TA1535、TA100、TA1537和TA98以及大肠杆菌WP2uvrA，在156.25 - 5000微克/平板的剂量范围内进行。无论有无代谢活化系统（S - 9混合液），该药物在任何测试菌株中均未显著增加回复菌落数。染色体畸变试验使用培养的中国仓鼠肺细胞（CHL/IU），在300 - 4800微克/毫升的剂量范围内进行。无论有无代谢活化，均未观察到染色体畸变细胞频率的显著增加。微核试验在Slc:ddY雄性小鼠的骨髓细胞中进行。小鼠通过腹腔注射单次给药，剂量分别为0、250、500、1000和2000毫克/千克。在任何剂量水平下，多染性红细胞微核频率均未显著增加。这些结果表明，水合蒙特瑞林在体外和体内均无致突变活性。
