Amethopterin, α-Methopterin, MTX.
• Mechanism of action
Methotrexate ( MTX ) is an analogue of folic acid which penetrates into cells via a specific
membrane transport system used by physiological folates.1 Inside the cell MTX rapidly binds
to and inhibits its target enzyme dihydrofolate reductase (DHFR), leading to the inhibition of
the syntheses of purines and pyrimidines. Intracellular folates exist physiologically in the
form of polyglutamates and MTX is also metabolised to polyglutamate forms. Recent data
suggest that the syntheses of purines and thymidylate can be stopped by direct inhibition
from dihydrofolate and MTX polyglutamates. Thus, following the inhibition of DHFR by
MTX, increasing levels of the dihydrofolate polyglutamates may directly block the
syntheses of these nucleotides, thus in addition to direct inhibition of DHFR by
methotrexate, the formation of polyglutamyl metabolites of the drug is also thought to...