Altretamine
Chemical compound
From Wikipedia, the free encyclopedia
Altretamine (trade name Hexalen), also called hexamethylmelamine, is an antineoplastic agent. It was approved by the U.S. FDA in 1990.
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| Trade names | Hexalen |
| Other names | 2,4,6-Tris(dimethylamino)-1,3,5-triazine |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601200 |
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| Routes of administration | Oral (capsules) |
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| Protein binding | 94% |
| Metabolism | Extensive liver |
| Metabolites | Pentamethylmelamine, tetramethylmelamine |
| Elimination half-life | 4.7–10.2 hours |
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| ECHA InfoCard | 100.010.391 |
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| Formula | C9H18N6 |
| Molar mass | 210.285 g·mol−1 |
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Uses
It is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with cisplatin and/or alkylating agent-based combination.[1]
It is not considered a first-line treatment,[2] but it can be useful as salvage therapy.[3] It also has the advantage of being less toxic than other drugs used for treating refractory ovarian cancer.[4]
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.[5]
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.[6]
Side effects
Side effects include nausea, vomiting, anemia and peripheral sensory neuropathy.[7]
Interactions
Combination with pyridoxine (vitamin B6) decreases neurotoxicity but has been found to reduce the effectiveness of an altretamine/cisplatin regime.[8] MAO inhibitor can cause severe orthostatic hypotension when combined with altretamine; and cimetidine can increase its elimination half-life and toxicity.[7]