Mechanism of action of mitoxantrone.
Mitoxantrone, a synthetic anthracenedione, was developed in the 1980s as a doxorubicin analogue in a program to find a cytotoxic agent with decreased cardiotoxicity compared with doxorubicin. It was approved by the FDA in 1987 for the treatment of adult acute myeloid leukemia and in 1996 for symptomatic hormone-refractory prostate cancer. In 2000, mitoxantrone was approved by the FDA for the treatment of worsening relapsing-remitting multiple sclerosis (MS), secondary progressive MS, and progressive-relapsing MS. Mitoxantrone is taken up rapidly by tissues, from which it is released slowly, and the terminal half-life ranges from 8.9 hours to 9 days. The highest concentrations of the drug are typically found in the thyroid, liver, and heart, and the drug persists in the body for as long as 272 days. Mitoxantrone is effective in reducing disease progression through a variety of different mechanisms of action. For example, it suppresses the proliferation of T cells, B cells, and macrophages. It impairs antigen presentation and decreases the secretion of proinflammatory cytokines. Mitoxantrone enhances T-cell suppressor function and inhibits B-cell function and antibody production. Finally, it inhibits macrophage-mediated myelin degradation. Compared with interferon betas, mitoxantrone has a broad range of actions and has effects on many different types of immune cells.
Fox
Edward J
EJ
MS Clinic of Central Texas, 7200 Wyoming Springs Dr., Suite 1100, Round Rock, TX 78681, USA. FoxTex@aol.com
D000818:Animals; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology; D008942:Mitoxantrone / Q000493:pharmacokinetics / Q000494:pharmacology*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D010455:Peptides / Q000494:pharmacology
D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D008942:Mitoxantrone