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Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin

  • Original Articles
  • Neurotoxicity, Dermatotoxicity, Cyanomorpholinyl Adriamycin
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Summary

The highly lipophilic cyanomorpholinyl adriamycin (CMA) is the most potent antineoplastic anthracycline yet described. CNS distribution and toxicity were examined after i.v. administration of CMA to mice. At doses ⩾0.1 mg/kg, a neurotoxic syndrome including ataxia, hypokinesia, and tremors appeared. At doses of ⩽0.05 mg/kg, which have been reported to be antineoplastic, no neurotoxicity was observed. On histopathologic examination, no changes were observed in the brain, spinal cord, or dorsal root ganglia. Unlike adriamycin (ADR), which rapidly appears in the nuclei of several tissues, CMA showed no fluorescence, suggesting a different cellular microcompartmentalization. The i.d. injection of CMA disclosed a 200-fold increase in toxicity compared with that of adriamycin. In comparisons of CMA and ADR, neurotoxicity and cardiotoxicity occurred equally only at higher doses; however, the dermatotoxicity and antineoplastic activity of CMA were increased several hundred-fold.

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Authors and Affiliations

  1. Department of Biochemistry, Comprehensive Cancer Center, University of Southern California, School of Medicine, 90033, Los Angeles, CA, USA

    Steven C. Cramer & Zoltán A. Tökés

  2. Department of Pathology, Comprehensive Cancer Center, University of Southern California, School of Medicine, 90033, Los Angeles, CA, USA

    Roy H. Rhodes

  3. M. D. Anderson Hospital, 77030, Houston, Texas, USA

    Edward M. Acton

  4. Tumor Institute, The University of Texas System Cancer Center, 77030, Houston, Texas, USA

    Edward M. Acton

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  1. Steven C. Cramer
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  2. Roy H. Rhodes
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  4. Zoltán A. Tökés
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Cramer, S.C., Rhodes, R.H., Acton, E.M. et al. Neurotoxicity and dermatotoxicity of cyanomorpholinyl adriamycin. Cancer Chemother. Pharmacol. 23, 71–75 (1989). https://doi.org/10.1007/BF00273520

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  • DOI: https://doi.org/10.1007/BF00273520

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