Lack of correlation between melanin affinity and retinopathy in mice and cats treated with chloroquine or flunitrazepam

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Abstract
Flunitrazepam (Rohypnol®, Roche, Basel, Switzerland), which is similar to chloroquine, has an affinity to melanin in retinal cells. However, in contrast to chloroquine, it does not induce structural alterations in these cells or in adjacent tissues of pigmented mice and cats even after treatment for 6 and 12 months with respectively, 2000-times (mice) or 130-times (cats) the effective human daily dose. Treatment with chloroquine (with a dose similar to that used in human anti-rheumatic therapy) over the same period, resulted in the appearance of numerous membranous cytoplasmic bodies in the retinal ganglion cells of mice and cats. In addition, in cats, an augmentation of lysosomal structures in the pigment epithelium, chiefly in the melanin-free region, and destruction of the tapetal cells were observed. Moreover, the pigment epithelium with the highest concentration of melanin was unaffected in mice and only slightly affected in cats. It was concluded that the retinotoxic effect of chloroquine is not the result of its affinity to melanincontaining tissues. Consequently, the affinity to melanin-containing cells per se is not sufficient to class a substance as potentially harmful to vision.