Altretamine

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Hexamethylmelamine
Skeletal formula of altretamine
Ball-and-stick model of the altretamine molecule
Systematic (IUPAC) name
N2,N2,N4,N4,N6,N6-hexamethyl-1,3,5-triazine-2,4,6-triamine
Clinical data
Trade names Hexalen
AHFS/Drugs.com monograph
MedlinePlus a601200
Licence data US FDA:link
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Legal status
Pharmacokinetic data
Protein binding 94%
Biological half-life 4.7-10.2 hours
Identifiers
CAS Number 645-05-6 YesY
ATC code L01XX03 (WHO)
PubChem CID: 2123
IUPHAR/BPS 7112
DrugBank DB00488 YesY
ChemSpider 2038 YesY
UNII Q8BIH59O7H YesY
KEGG D02841 YesY
ChEBI CHEBI:24564 YesY
ChEMBL CHEMBL1455 YesY
Chemical data
Formula C9H18N6
Molecular mass 210.28 g/mol
  • n1c(nc(nc1N(C)C)N(C)C)N(C)C
  • InChI=1S/C9H18N6/c1-13(2)7-10-8(14(3)4)12-9(11-7)15(5)6/h1-6H3 YesY
  • Key:UUVWYPNAQBNQJQ-UHFFFAOYSA-N YesY
  (verify)

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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  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ "Foy`s principles of Medical chemistry", edited by Thomas L. Lemke, sixth edition, 2008, 1162 pages, ISBN 978-0-7817-6879-5.
  6. ↑ 6.0 6.1 Drugs.com: Altretamine Monograph
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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