Accumulation of substances with melanin affinity to the internal ear. Therapeutic or ototoxic mechanism?

The capacity of the melanin in the internal ear to accumulate and retain labelled lidocaine, bupivacaine and chlorpromazine after intravenous and intraperitoneal injection was examined by whole-body autoradiography. Both young pigmented hooded rats and albino rats were studied. In the pigmented rats chlorpromazine showed the greatest accumulation, which was more pronounced in the cochlea than in the vestibular portion. The other two substances were evenly distributed in the internal ear. After a single injection of chlorpromazine and of bupivacaine these substances were still bound to the melanin of the internal ear after 14 days, which was the longest survival time. Lidocaine, on the other hand, had disappeared after only 4 days. In albino animals there was very weak, transient uptake of chlorpromazine and bupivacaine, but not of lidocaine, in the internal ear. In studies in vitro on isolated bovine eye melanin there was considerably greater adsorption of chlorpromazine than of lidocaine and bupivacaine.