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Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs

  • Original Articles
  • Acridine Antitumor Agents, Blood-Brain Barrier, Liver
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Summary

The blood-brain barrier penetration of amsacrine and its analogs 9-({2-methoxy-4-[(methylsulfonyl)-amino]phenyl}amino)-,5-dimethyl-4-acridine carboxamide (CI-921) and M-[2-(dimethylamino)ethyl]-acridine-4-carboxamide (AC) was measured in the barbiturate-anesthetized mouse. After intracarotid administration, AC was almost completery extracted (90%) in a single transit through the brain capillaries, whereas CI-921 (20%) and amsacrine (15%) were moderately extracted. AC is retained in the brain; no loss of AC from the brain was apparent at 1, 2, 4, or 8 min after injection. In contrast, after intraportal administration, 75% of the AC, 94% of the CI-921, and 57% of the amsacrine was extracted in a single transit through the hepatic vasculature. Rather than being retained in the mouse liver, these acridine antitumor agents show time-dependent loss (t 1/2=10 min for amsacrine and AC, 24 min for CI-921). We conclude that unlike most antitumor agents, these acridine drugs appear to penetrate the blood-brain barrier readily.

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Authors and Affiliations

  1. Southwestern Regional V. A. Epilepsy Center, Research and Neurology Services, Veterans Administration West Los Angeles Medical Center, 90073, Los Angeles, CA, USA

    Eain M. Cornford

  2. Department of Neurology, Brain Research Institute, UCLA School of Medicine, 90024, Los Angeles, CA, USA

    Eain M. Cornford

  3. Department of Pharmacology and Clinical Pharmacology, Auckland University School of Medicine, Auckland, New Zealand

    Deborah Young & James W. Paxton

Authors
  1. Eain M. Cornford
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  2. Deborah Young
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  3. James W. Paxton
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Additional information

This study was supported by the Auckland Medical Research Foundation (New Zealand), by the Medical Research Foundation (New Zealand), by the National Science Foundation (United States/New Zealand Cooperative Science Program), by the United States Veterans Administration, and by NIH grant NS 25554

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Cornford, E.M., Young, D. & Paxton, J.W. Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs. Cancer Chemother. Pharmacol. 29, 439–444 (1992). https://doi.org/10.1007/BF00684844

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  • DOI: https://doi.org/10.1007/BF00684844

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