Altretamine
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Altretamine (also hexalen) is an antineoplastic agent. It was approved by the FDA in 1990.
Uses
It is used to treat refractory ovarian cancer.
It is not considered a first-line treatment,[1] but it can be useful as salvage therapy.[2] It also has the advantage of being less toxic than other drugs used for treating refractory ovarian cancer.[3]
Mechanism
The precise mechanism by which altretamine exerts its anti-cancer effect is unknown but it is classified by MeSH as an alkylating antineoplastic agent.[4] This unique structure is believed to damage tumor cells through the production of the weakly alkylating species formaldehyde, a product of CYP450-mediated N-demethylation. Administered orally, altretamine is extensively metabolized on first pass, producing primarily mono- and didemethylated metabolites. Additional demethylation reactions occur in tumor cells, releasing formaldehyde in situ before the drug is excreted in the urine. The carbinolamine (methylol) intermediates of CYP450-mediated metabolism also can generate electrophilic iminium species that are capable of reacting covalently with DNA guanine and cytosine residues as well as protein. Iminium-mediated DNA cross-linking and DNA-protein interstrand cross-linking, mediated through both the iminium intermediate and formaldehyde, have been demonstrated, although the significance of DNA cross-linking on altretamine antitumor activity is uncertain.[5]
Side effects
Side effects include nausea, vomiting, anemia and peripheral sensory neuropathy.[6]
Interactions
Combination with pyridoxine (vitamin B6) decreases neurotoxicity but has been found to reduce the effectiveness of an altretamine/cisplatin regime.[7] MAO inhibitor can cause severe orthostatic hypotension when combined with altretamine; and cimetidine can increase its elimination half-life and toxicity.[6]
See also
References
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- ↑ "Foy`s principles of Medical chemistry", edited by Thomas L. Lemke, sixth edition, 2008, 1162 pages, ISBN 978-0-7817-6879-5.
- ↑ 6.0 6.1 Drugs.com: Altretamine Monograph
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