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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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| Pharmacokinetic data | |
| Protein binding | 94% |
| Metabolism | Extensiveliver |
| Metabolites | Pentamethylmelamine, tetramethylmelamine |
| Eliminationhalf-life | 4.7–10.2 hours |
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| ECHA InfoCard | 100.010.391 |
| Chemical and physical data | |
| Formula | C9H18N6 |
| Molar mass | 210.285 g·mol−1 |
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Altretamine (trade nameHexalen), also calledhexamethylmelamine, is anantineoplastic agent. It was approved by theU.S. FDA in 1990.
It is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrentovarian cancer following first-line therapy withcisplatin and/oralkylating agent-based combination.[1]
It is not considered a first-line treatment,[2] but it can be useful assalvage therapy.[3] It also has the advantage of being less toxic than other drugs used for treating refractory ovarian cancer.[4]
The precise mechanism by which altretamine exerts its anti-cancer effect is unknown but it is classified byMeSH as analkylating antineoplastic agent.[5]
This unique structure is believed to damagetumor cells through the production of the weakly alkylating speciesformaldehyde, a product ofCYP450-mediatedN-demethylation. Administered orally, altretamine is extensively metabolized on first pass, producing primarily mono- and didemethylated metabolites. Additional demethylation reactions occur in tumor cells, releasingformaldehyde in situ before the drug is excreted in the urine. Thecarbinolamine (methylol) intermediates of CYP450-mediated metabolism also can generate electrophilic iminium species that are capable of reacting covalently with DNAguanine andcytosine 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 includenausea,vomiting,anemia andperipheral sensory neuropathy.[7]
Combination withpyridoxine (vitamin B6) decreasesneurotoxicity but has been found to reduce the effectiveness of an altretamine/cisplatin regime.[8]MAO inhibitor can cause severeorthostatic hypotension when combined with altretamine; andcimetidine can increase its elimination half-life and toxicity.[7]
