Mechanism of action of mitoxantrone
- PMID: 15623664
- DOI: 10.1212/wnl.63.12_suppl_6.s15
Mechanism of action of mitoxantrone
Abstract
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.
Similar articles
-
Mitoxantrone: a review of its use in multiple sclerosis.CNS Drugs. 2004;18(6):379-96. doi: 10.2165/00023210-200418060-00010. CNS Drugs. 2004. PMID: 15089110 Review.
-
Current approved options for treating patients with multiple sclerosis.Neurology. 2004 Dec 28;63(12 Suppl 6):S8-14. doi: 10.1212/wnl.63.12_suppl_6.s8. Neurology. 2004. PMID: 15623672 Review.
-
Pharmacokinetics and pharmacodynamics of the interferon-betas, glatiramer acetate, and mitoxantrone in multiple sclerosis.J Neurol Sci. 2007 Aug 15;259(1-2):27-37. doi: 10.1016/j.jns.2006.05.071. Epub 2007 Mar 27. J Neurol Sci. 2007. PMID: 17391705 Review.
-
Mechanisms of mitoxantrone in multiple sclerosis--what is known?J Neurol Sci. 2004 Aug 15;223(1):25-7. doi: 10.1016/j.jns.2004.04.015. J Neurol Sci. 2004. PMID: 15261556 Review.
-
Management of worsening multiple sclerosis with mitoxantrone: a review.Clin Ther. 2006 Apr;28(4):461-74. doi: 10.1016/j.clinthera.2006.04.013. Clin Ther. 2006. PMID: 16750460 Review.
Cited by
-
Targeting Chemokines and Chemokine Receptors in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.J Inflamm Res. 2020 Sep 29;13:619-633. doi: 10.2147/JIR.S270872. eCollection 2020. J Inflamm Res. 2020. PMID: 33061527 Free PMC article. Review.
-
Differential Effects of MS Therapeutics on B Cells-Implications for Their Use and Failure in AQP4-Positive NMOSD Patients.Int J Mol Sci. 2020 Jul 16;21(14):5021. doi: 10.3390/ijms21145021. Int J Mol Sci. 2020. PMID: 32708663 Free PMC article. Review.
-
Pre-existing T- and B-cell defects in one progressive multifocal leukoencephalopathy patient.PLoS One. 2012;7(4):e34493. doi: 10.1371/journal.pone.0034493. Epub 2012 Apr 4. PLoS One. 2012. PMID: 22496817 Free PMC article.
-
Immunogenic chemotherapy: great potential for improving response rates.Front Oncol. 2023 Dec 6;13:1308681. doi: 10.3389/fonc.2023.1308681. eCollection 2023. Front Oncol. 2023. PMID: 38125944 Free PMC article. Review.
-
T-cell based immunotherapy in experimental autoimmune encephalomyelitis and multiple sclerosis.Immunotherapy. 2010 Jan;2(1):99-115. doi: 10.2217/imt.09.61. Immunotherapy. 2010. PMID: 20231863 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
