MUTAGENICITY STUDIES OF RCC-36, THE ACTIVE METABOLITE OF (±)-4-DIETHYLAMINO-1, 1-DIMETHYLBUT-2-YN-1-YL 2-CYCLOHEXYL-2-HYDROXY-2-PHENYLACETATE MONOHYDROCHLORIDE MONOHYDRATE (NS-21), A NOVEL DRUG FOR URINARY FREQUENCY AND INCONTINENCE

The mutagenicity of (±)-4-ethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride (RCC-36), an active metabolite of (±)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), was investigated by the reverse mutation test in bacteria, the chromosome aberration test in vitro, and the micronucleus test in mice. The reverse mutation test was performed at a dose range of 6.25-400 μg/plate using Salmonella typhimurium TA100, TA1535, TA98, and TA1537, and Escherichia coli WP2uvrA. RCC-36 did not increase revertant colonies significantly in any of the test strains with or without metabolic activation system (S9 mix). The chromosome aberration test was carried out at a dose range of 2.5-20 μg/ml without S9 mix and 10-80 μg/ml with S9 mix using cultured Chinese hamster lung cells (CHL/IU). No significant increases of the frequencies of cells with chromosome aberrations were observed with or without S9 mix. The micronucleus test was conducted in the bone marrow cells of Slc:ddY male mice. Mice were given RCC-36 by a single intraperitoneal administration at doses of 0, 10, 20, 40, and 80 mg/kg. There were no significant increases in the frequencies of micronucleated polychromatic erythrocytes at any dose levels. These results show that RCC-36 has no mutagenic activity in vitro or in vivo.