Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI0C2YLFG)
  Drug Name Tranylcypromine Drug Info Methyldopa Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antihypertensive Agents
  Structure

 Mechanism of Tranylcypromine-Methyldopa Interaction (Severity Level: Major)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tranylcypromine Methyldopa
      Mechanism Monoamine oxidase inhibitor Monoamine oxidase substrate
      Key Mechanism Factor 1
Factor Name Monoamine oxidase Structure Sequence
Protein Family Flavin monoamine oxidase family
Protein Function
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Methyldopa caused by Tranylcypromine mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Concurrent use of methyldopa with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine) is considered contraindicated. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with methyldopa.

References
1 Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31. [PMID: 8845455]
2 De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5. [PMID: 4379192]
3 Paykel ES "Hallucinosis on combined methyldopa and pargyline." Br Med J 1 (1966): 803. [PMID: 5910115]
4 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
5 Product Information. Aldomet (methyldopa). Merck & Co, Inc, West Point, PA.
6 Schulz R, Antonin KH, Hoffmann E, et al "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36. [PMID: 2510962]
7 van Rossum JM "Potential danger of monoamineoxidase inhibitors and a-methyldopa." Lancet 1 (1963): 950-1. [PMID: 13975251]
8 van Rossum JM, Hurkmans JA "Reversal of the effect of a-Methyldopa by monamine oxidase inhibitors." J Pharm Pharmacol 15 (1963): 493-9. [PMID: 14059015]