Drug General Information (ID: DDIPKOE402)
  Drug Name Cyproheptadine Drug Info Tranylcypromine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihistamines Antidepressants
  Structure

 Mechanism of Cyproheptadine-Tranylcypromine Interaction (Severity Level: Moderate)
     Antagonize the effect of serotonergic agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Cyproheptadine Tranylcypromine
      Mechanism 1 Antiserotonergic effects
5-HT 2 receptor  Antagonist
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
  • Antagonize the effect of Tranylcypromine when combined with Cyproheptadine 
      Mechanism 2 Antiserotonergic effects
5-HT 2 receptor  Inhibitor
Serotonergic effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 3
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 4
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
  • Antagonize the effect of Tranylcypromine when combined with Cyproheptadine 

Recommended Action
      Management Patients should be monitored for potentially diminished therapeutic response to MAOIs and increased antihistaminic effects of cyproheptadine during coadministration. Discontinuation of cyproheptadine may be necessary if an interaction is suspected.

References
1 Kahn DA "Possible toxic interaction between cyproheptadine and phenelzine." Am J Psychiatry 144 (1987): 1242-3. [PMID: 3631331]
2 Katz RJ, Rosenthal M "Adverse interaction of cyproheptadine with serotonergic antidepressants." J Clin Psychiatry 55 (1994): 314-5. [PMID: 8071295]
3 Product Information. Periactin (cyproheptadine). Merck & Co, Inc, West Point, PA.
4 Zubieta JK, Demitrack MA "Depression after cyproheptadine: MAO treatment ." Biol Psychiatry 31 (1992): 1177-8. [PMID: 1525285]