Methotrexate is a cell cycle arresting agent with varying effects. Methotrexate arrests the cell cycle in late G1/S-phase, therefore inhibiting the synthesis of DNA, RNA, thymidylates, and proteins. In the previous cases the inhibition of enzymes involved in purine metabolism, leading to accumulation of adenosine, or the suppression of intercellular adhesion molecule expression by T cells as the main mechanism of action by methotrexate. The compound has been observed to irreversibly inhibit dihydrofolate reductase (DHFR) and thymidylate synthetase (TS). Methotrexate has been shown to modulate inflammation by promoting adenosine release or inhibiting transmethylation reactions. In adherent splenic cells, IL-1 production was decreased by methorexate.
Methotrexate