Investigations into the Cataractogenic Potency of a Non-Tricyclic Antidepressant

During the preclinical development of a non-tricyclic antidepressant, lens changes were observed in a 13-week subacute toxicity study. They consisted of radial striations, a prominent anterior suture and focal opacities in the posterior lens cortex. No such lens changes were observed in beagle dogs during the same study period. To get an insight into the doseresponse characteristics of this cataractogenic potential of the compound during 26-week chronic toxicity studies, Scheimpflug photography has been performed in albino rats and beagle dogs. Parallel to slit lamp examinations, changes in lens density were recorded with the SL-45 on 2 occasions, at baseline and end of the study. The images were recorded on T-Max 400 (BW) film, developed and evaluated according to standard procedures. The density data of the capsular region of the rat lens evidence a significant increase in density in group 4 (highest dose) in male and female animals at the last examination, as compared to group 1 (control) and group 2 (lowest dose). As there were no visible cataracts in a majority of lenses of group 4 yet, the data evidence a subliminal cataractogenic potential, on the borderline of being direct. The other 2 groups did not show a density increase, as compared to group 1. No animal of the beagle dog study did have an increase in lens light scattering over the study period. The data from the chronic toxicity studies evidence a cataractogenic potential in rats present at toxic respectively even lethal dosage levels. The 2 lower dosages were free of this potential. The clinical observations support these data.