Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIGH2JIZO)
  Drug Name Fenfluramine Drug Info Methylene blue Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Cns Stimulants Antidotes/Mao Inhibitors
  Structure

 Mechanism of Fenfluramine-Methylene blue Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Fenfluramine Methylene blue
      Mechanism Serotonergic effects
5-HT 2 receptor  Agonist 		Serotonergic effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 1
Factor Name 5-HT 2 receptor Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538). Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:28129538). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.
    Click to Show/Hide
      Key Mechanism Factor 2
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
  • Additive serotonergic effects by the combination of Fenfluramine and Methylene blue 

Recommended Action
      Management Serotonergic agents should not be used in patients receiving methylene blue intravenously. Most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with methylene blue if possible, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life.

References
1 Boyer EW, Shannon M "The serotonin syndrome." N Engl J Med 352 (2005): 1112-20. [PMID: 15784664]
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Gillman PK "Methylene blue and serotonin toxicity: definite causal link." Psychosomatics 51 (2010): 448-9. [PMID: 20833947]
4 Gillman PK "Methylene blue is a potent monoamine oxidase inhibitor." Can J Anaesth 55 (2008): 311-2 author reply 312. [PMID: 18451123]
5 Heritier Barras AC, Walder B, Seeck M "Serotonin syndrome following Methylene Blue infusion: a rare complication of antidepressant therapy." J Neurol Neurosurg Psychiatry 81 (2010): 1412-3. [PMID: 20547626]
6 Khavandi A, Whitaker J, Gonna H "Serotonin toxicity precipitated by concomitant use of citalopram and methylene blue." Med J Aust 189 (2008): 534-5. [PMID: 18976207]
7 Ng BK, Cameron AJ "The role of methylene blue in serotonin syndrome: a systematic review." Psychosomatics 51 (2010): 194-200. [PMID: 20484716]
8 Ng BK, Cameron AJ, Liang R, Rahman H. Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review.?Can J Anaesth. 2008;55(1):36-41. [PMID: 18166746]
9 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Serious CNS reactions possible when linezolid (Ayvox) is given to patients taking certain psychiatric medications.".
10 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications.".