C Hewett, J Ellenberger, H Köllmer, H Kreuzer, A Niggeschulze, H Stötzer
Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin), a new hypnotic, was submitted to a comprehensive range of safety assessment tests. Acute (single dose) toxicity was very low, while in subacute and chronic studies in rodents, signs of toxicity were first seen at doses of 400 mg/kg or more. Histopathological changes were only seen in the 1 1/2-year study. Ataxia, salivation, and diarrhea were observed in a 4-week intravenous study in dogs, and ataxia, increased feed intake, muscular spasms, increased liver weight, and lipid depletion of the adrenal cortex in two oral studies in monkeys...
March 1986: Arzneimittel-Forschung