With news that a laboratory in New York State has identified the rodenticide aminopterin in the recalled foods, catmanager started looking for information on this chemical.

The Wikipedia article on aminopterin states

Aminopterin (4-aminopteroic acid), a 4-amino analog of folic acid, is an antineoplastic drug with immunosuppressive properties used in chemotherapy. Aminopterin is a synthetic derivative of pterin. Aminopterin works by competing for the folate binding site of the enzyme dihydrofolate reductase. Its binding affinity for dihydrofolate reductase effecticely blocks tetrahydrofolate synthesis. This results in the depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis.

Aminopterin has been used to treat leukemia in children, but the use was discontinued because of its “unpredictable toxicity.” It is currently being tested in a purer form as a leukemia treatment.

Aminopterin has also been used as an abortifacient but was shown to cause fetal malformations.

The EPA’s aminopterin chemical profile is here. Aminopterin is not currently registered as a rodenticide in the United States.

Another government fact sheet is here.

Information from the Comparative Toxicogenomics Database is here.

An NIH fact sheet is here.

PubMed lists several studies from the 1950s on reversing aminopterin toxicity (because the studies are that far back, no abstracts are available online):

  • Barnard, RD, and MD Freeman, Aminopterin toxicity reversal by a hemopoietic fraction of microbial animal protein factor: some similarities of streptomyces fermentation residue to pituitary erythropoietin, Am J Dig Dis. 1955 Mar;22(3):76–82.
  • Barnard, RD, and MD Freeman, Reversal of aminopterin toxicity by water-soluble cupridihydroporphyrins (chloresium), Am J Dig Dis. 1954 Jun;21(6):163–9.
  • Reversal of aminopterin toxicity in the rat, Nutr Rev. 1953 Nov;11(11):348–50.
  • Sauberlich, HE, Studies on the reversal of aminopterin toxicity in the rat with citrovorum factor, folacin and related compounds, J Nutr. 1953 May;50(1):101–15.

This is from a study published in Molecular Pharmacology in 2004:

The pharmacology of aminopterin raises questions about decreased solubility and precipitation as a cause of antifolate nephrotoxicity. Aminopterin is more soluble than methotrexate in urine at 37°C and 10-fold more potent than methotrexate in inhibiting dihydrofolate reductase. On the basis of the precipitation theory of antifolate nephrotoxicity, aminopterin should be less toxic than methotrexate. Although Glode et al. (1979) predicted that aminopterin would be more efficacious and less nephrotoxic than methotrexate, they found that 50% of patients who received aminopterin without hydration developed dose-limiting nephrotoxicity. Two patients who died from renal failure lacked aminopterin precipitates in the kidney at autopsy, and these authors suggested that antifolates may cause nephrotoxicity independent of renal precipitation. In contrast, our theory of renal antifolate elimination predicts that aminopterin would be more nephrotoxic than methotrexate. Renal FRs had higher affinities for aminopterin than for methotrexate at every pH tested. Although hydration and alkalinization decreased aminopterin toxicity (Glode et al., 1979), the efficacy of hydration alone in decreasing nephrotoxicity was not tested.

Given the antineoplastic and teratogenic characteristics of aminopterin, veterinarians might need to watch carefully for immunosuppression in patients that have ingested the contaminated food and counsel owners of bitches and queens on the possibility of congenital malformation.

Update: VIN has a publicly available information sheet here.

Also, in case you were wondering about the pronunciation of aminopterin, it’s am-i-nop-tur-in (you can hear it pronounced on the Merriam-Webster Web site). During his appearance on CNN, Dr. Jeff Weber pronounced it uh-me-no-tare-in. The root word pter- is pronounced “tare” in words like pterodactyl, so Dr. Weber’s pronunciation is understandable. However, all the dictionaries I checked give the same pronunciation as Merriam-Webster.

Finally, aminopterin is derived from pterin, a compound that is found in the pigments that enable butterflies to have such colorful wings.