Quick Shot #12 Answer
Answer: Methotrexate – direct antagonist of purine metabolism
Methotrexate is a folate anti-metabolite that inhibits aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase (ATIC) and dihydrofolate reductase. This leads to an accumulation of adenosine deaminase and then indirectly to decreased purine synthesis which results in impaired DNA repair and cell cycle replication. This in turn leads to a decreased immune response. Azathioprine on the other hand is a purine analog which directly antagonizes purine synthesis.
- Egan LJ, Sandborn WJ. Methotrexate for inflammatory bowel disease: pharmacology and preliminary results. Mayo Clin Proc. 1996 Jan;71(1):69-80. doi: 10.4065/71.1.69. PMID: 8538238.
- Patel V, Wang Y, MacDonald JK, McDonald JW, Chande N. Methotrexate for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2014 Aug 26;2014(8):CD006884. doi: 10.1002/14651858.CD006884.pub3. PMID: 25157445; PMCID: PMC8202560.