Pre-clinical toxicity studies on the new nitroimidazole 1-methylsulphonyl-3-(1-methyl-5-nitroimidazole-2-yl)-2- imidazolidinone.
Administration of 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazole-yl)-2-imidazolidinone (Go 10213) at a dose of 5000 mg/kg to rat, mouse, guinea pig and rabbit and 3000 mg/kg to dog did not induce any toxic symptoms or mortality. Repeated daily gavaging with doses ranging from 50-3000 mg/kg/day were tolerated by rats for 2 weeks. No mortality was noticed in treated animals. Reduction in weight gain was observed in male rats on 2000 mg/kg per day and females on 1000 mg/kg per day. No toxic changes were noticed in dogs treated with 200 mg/kg per day for 2 weeks. One monkey treated with 75 mg/kg per day for 4 weeks tolerated the compound without exhibiting any toxic effects. No drug induced alterations were noticed in rats gavaged with 60 and 200 mg/kg per day for 4 weeks. Rats treated with a daily dose of 600 mg/kg showed reduction in body weight gain and atrophy of testes and these changes were reversible after stopping of medication. Dogs medicated with 30 and 100 mg/kg per day tolerated the drug for 4 weeks. Except slight ataxia in a few dogs treated with 100 mg/kg per day, no other drug induced toxic effects were noticed. Neurological symptoms were noticed in all dogs on high dose of 200 mg/kg. Three animals out of six were sacrificed in extremis in this dose. After discontinuation of Go 10213 all dogs on 100 and 200 mg/kg per day recovered normal gait in about a week. No definitive drug induced changes were noticed in laboratory investigations, gross and histopathological examinations.(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000633:toxicity*; D004285:Dogs; D004334:Drug Administration Schedule; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced; D009593:Nitroimidazoles / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D013091:Spermatogenesis / Q000187:drug effects
D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; C034473:satranidazole