PHARMACOLOGIC ANTIDOTES TO EXPERIMENTAL DOXORUBICIN SKIN TOXICITY - A SUGGESTED ROLE FOR BETA-ADRENERGIC COMPOUNDS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 65  (11-1) , 1001-1006
Abstract
Doxorubicin (ADM) skin toxicity is a serious complication of inadvertent perivenous drug infiltrations. In an attempt to identify possible antidotes, 9 diverse pharmacologic agents were injected intradermally into the hair-free dorsum of BALB/c mice following an intradermal ADM dose of 0.05 or 0.5 mg. Seven of the compounds were ineffective in reducing ADM-induced ulceration; the compounds included lidocaine, cimetidine, diphenhydramine, sodium heparin, hyaluronidase, N-acetylcysteine and .alpha.-tocopherol. The latter 5 compounds actually increased ulceration induced by ADM (0.5 mg), especially N-acetylcysteine, which tripled the total toxic effect. Two opposing .beta.-adrenergic compounds, the antagonist propranolol and the agonist isoproterenol, reduced skin ulceration resulting from experimental treatment with intradermal ADM. A role for the .beta.-adrenergic receptor in mediating ADM-induced skin ulceration is suggested. [ADM is used in cancer chemotherapy.].

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