Altretamine

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Altretamine
Altretamine Structural Formulae V.1.svg
Systematic (IUPAC) name
N2,N2,N4,N4,N6,N6-hexamethyl-1,3,5-triazine-2,4,6-triamine
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a601200
Pregnancy cat. D (AU) D (US)
Legal status Prescription Only (S4) (AU) -only (CA) -only (US)
Pharmacokinetic data
Protein binding 94%
Half-life 4.7-10.2 hours
Identifiers
CAS number 645-05-6 YesY
ATC code L01XX03
PubChem CID 2123
DrugBank DB00488
ChemSpider 2038 YesY
UNII Q8BIH59O7H YesY
KEGG D02841 YesY
ChEBI CHEBI:24564 YesY
ChEMBL CHEMBL1455 YesY
Chemical data
Formula C9H18N6 
Mol. mass 210.28 g/mol
 YesY (what is this?)  (verify)

Altretamine (also hexalen) is an antineoplastic agent. It was approved by the FDA in 1990.

Uses[edit]

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[edit]

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[edit]

Side effects include nausea, vomiting, anemia and peripheral sensory neuropathy.[6]

Interactions[edit]

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[edit]

References[edit]

  1. ^ Keldsen N, Havsteen H, Vergote I, Bertelsen K, Jakobsen A (2003). "Altretamine (hexamethylmelamine) in the treatment of platinum-resistant ovarian cancer: a phase II study". Gynecol. Oncol. 88 (2): 118–22. doi:10.1016/S0090-8258(02)00103-8. PMID 12586589. 
  2. ^ Chan JK, Loizzi V, Manetta A, Berman ML (2004). "Oral altretamine used as salvage therapy in recurrent ovarian cancer". Gynecol. Oncol. 92 (1): 368–71. doi:10.1016/j.ygyno.2003.09.017. PMID 14751188. 
  3. ^ Malik IA (2001). "Altretamine is an effective palliative therapy of patients with recurrent epithelial ovarian cancer". Jpn. J. Clin. Oncol. 31 (2): 69–73. doi:10.1093/jjco/hye012. PMID 11302345. 
  4. ^ Damia G, D'Incalci M (1995). "Clinical pharmacokinetics of altretamine". Clinical pharmacokinetics 28 (6): 439–48. doi:10.2165/00003088-199528060-00002. PMID 7656502. 
  5. ^ "Foy`s principles of Medical chemistry", edited by Thomas L. Lemke, sixth edition, 2008, pages=1162, ISBN=978-0-7817-6879-5.
  6. ^ a b Drugs.com: Altretamine Monograph
  7. ^ Wiernik, P. H.; Yeap, B.; Vogl, S. E.; Kaplan, B. H.; Comis, R. L.; Falkson, G.; Davis, T. E.; Fazzini, E.; Cheuvart, B.; Horton, J. (1992). "Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: A study of the Eastern Cooperative Oncology Group". Cancer investigation 10 (1): 1–9. doi:10.3109/07357909209032783. PMID 1735009.  edit