Levels of reduced glutathione and potassium ion were determined in rabbit lenses after incubation in uitro in the presence of various compounds. After rabbit lenses had been incubated in uitro with 4-[3-(7-chloro-5,ll-dihydrodibenz[b,e][l,4]oxazepin-5-yl)propyl]-l-piperazineethanol hydrochloride (I), the levels of reduced glutathione and potassium ion were lower than after incubation with the corresponding 3-chloro analog (II).
Compound I was also more potent than I1 in producing the hemolysis of rabbit erythrocytes. The loss of reduced glutathione and potassium ion from the lens, as mediated by I and 5-[(2-dimethylamino)ethyl]-5,11-dihydrodibenz[b,e][l,4]oxazepine maleate (IV), was correlated with the tendency of these compounds to bind to erythrocyte ghosts. Levels of reduced glutathione were also examined in the lenses of rats that had been given chronic doses in the diet of either of two substituted dibenzoxazepines (I or its trifluoromethyl analog, III). After being dosed with either compound, the lowest levels of reduced glutathione were found in the lenses of those rats that had developed morphological changes of the greatest severity. 14C-Labeled compounds, both tricyclic and nontricyclic, were given orally to rabbits, and all of these compounds, whether or not they were cataractogenic, were found to be distributed in various portions of the eye. No chemical interaction was found between the substituted dibenzoxazepines and reduced glutathione when studies were conducted in uitro.
Keyphrases Dibenzoxazepines, substituted-effect on reduced glutathione and potassium-ion levels in rabbit and rat lenses, relationship to cataractogenicity o Glutathione, reduced-possible interaction with substituted dibenzoxazepines, significance to cataractogenicity Cataractogenicity-effect of substituted dibenzoxazepines on levels of reduced glutathione and potassium ions in lenses of iabbits in uitro and of rats in uiuo Potassium ionseffect of substituted dibenzoxazepines, rabbit and rat lenses Model 143, Instrumentation Laboratory. Inc Charles River CD. Rockland rat chow.
' NCS Amersharn/Searle. a Drugs were present at 2 X 10 -4 M . The rabbits weighed 2.2-2.8 kg.