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  • Title: Melanin capacity to accumulate drugs in the internal ear. A study on lidocaine, bupivacaine and chlorpromazine.
    Author: Lyttkens L, Larsson B, Göller H, Englesson S, Stahle J.
    Journal: Acta Otolaryngol; 1979; 88(1-2):61-73. PubMed ID: 474122.
    Abstract:
    The distribution and retention of labelled lidocaine, bupivacaine, and chlorpromazine to melanin in the internal ear after intravenous and intraperitoneal injection were 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. Strong uptake and retention of the three substances were observed in the eyes of pigmented animals. In albino animals there was very weak, transient uptake in the internal ear of chlorpromazine and bupivacaine, but not of lidocaine. In studies in vitro on isolated bovine eye melanin there was considerably greater adsorption of chlorpromazine than of lidocaine and bupivacaine. An uptake was noted in the human eye in experiments in vitro. Clinical tests revealed no acute or late damage to hearing or sight after large doses of lidocaine. The participation of melanin in different basal labyrinthine functions such as the energy transfer mechanism and the sound protective mechanism is discussed in the light of the results obtained. Further, the theory is put forward that the melanin affinity of certain substances can be of both therapeutic and ototoxic importance.
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