Drug General Information (ID: DDI4X3FEDI)
  Drug Name Methylergometrine Drug Info Lorcaserin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Oxytocics Anorexiants
  Structure

 Mechanism of Methylergometrine-Lorcaserin Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Methylergometrine Lorcaserin
      Mechanism 1 Serotonergic effects
5-HT 2B receptor  Agonist
Serotonergic effects
5-HT 2C receptor  Agonist
      Key Mechanism Factor 1
Factor Name 5-hydroxytryptamine receptor 2B
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Structure Sequence
MALSYRVSELQSTIPEHILQSTFVHVISSNWSGLQTESIPEEMKQIVEEQGNKLHWAALLILMVIIPTIGGNTLVILAVSLEKKLQYATNYFLMSLAVADLLVGLFVMPIALLTIMFEAMWPLPLVLCPAWLFLDVLFSTASIMHLCAISVDRYIAIKKPIQANQYNSRATAFIKITVVWLISIGIAIPVPIKGIETDVDNPNNITCVLTKERFGDFMLFGSLAAFFTPLAIMIVTYFLTIHALQKKAYLVKNKPPQRLTWLTVSTVFQRDETPCSSPEKVAMLDGSRKDKALPNSGDETLMRRTSTIGKKSVQTISNEQRASKVLGIVFFLFLLMWCPFFITNITLVLCDSCNQTTLQMLLEIFVWIGYVSSGVNPLVYTLFNKTFRDAFGRYITCNYRATKSVKTLRKRSSKIYFRNPMAENSKFFKKHGIRNGINPAMYQSPMRLRSSTIQSSSIILLDTLLLTENEGDKTEEQVSYV
Gene Name HTR2B
Uniprot ID 5HT2B_HUMAN
KEGG Pathway hsa:3357
Protein Family G-protein coupled receptor 1 family
Protein Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:8143856, PubMed:7926008, PubMed:8078486, PubMed:8882600, PubMed:18703043, PubMed:23519210). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:8143856, PubMed:7926008, PubMed:8078486, PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, PubMed:24357322, 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:8143856, PubMed:8078486, PubMed:8882600, PubMed:23519215, PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:23519215, PubMed:28129538). Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores (PubMed:8143856, PubMed:8078486, PubMed:8882600, PubMed:18703043, PubMed:23519215, PubMed:28129538). Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain (By similarity). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine (By similarity).
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      Key Mechanism Factor 2
Factor Name 5-hydroxytryptamine receptor 2C
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Structure Sequence
MVNLRNAVHSFLVHLIGLLVWQSDISVSPVAAIVTDIFNTSDGGRFKFPDGVQNWPALSIVIIIIMTIGGNILVIMAVSMEKKLHNATNYFLMSLAIADMLVGLLVMPLSLLAILYDYVWPLPRYLCPVWISLDVLFSTASIMHLCAISLDRYVAIRNPIEHSRFNSRTKAIMKIAIVWAISIGVSVPIPVIGLRDEEKVFVNNTTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYVLRRQALMLLHGHTEEPPGLSLDFLKCCKRNTAEEENSANPNQDQNARRRKKKERRPRGTMQAINNERKASKVLGIVFFVFLIMWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVCSGINPLVYTLFNKIYRRAFSNYLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTNEPVIEKASDNEPGIEMQVENLELPVNPSSVVSERISSV
Gene Name HTR2C
Uniprot ID 5HT2C_HUMAN
KEGG Pathway hsa:3358
Protein Family G-protein coupled receptor 1 family
Protein Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
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      Mechanism Description
  • Additive serotonergic effects by the combination of Methylergometrine and Lorcaserin 
     Increased risk of other adverse reactions (Unspecific) Click to Show/Hide Mechanism Graph
      Drug Name Methylergometrine Lorcaserin
      Mechanism 2 Risk of valvular heart disease Risk of valvular heart disease
      Key Mechanism Factor 3
Factor Name Adverse reactions
Factor Description An adverse reaction is an unexpected negative reaction to a medication or treatment that happens even when it's used correctly.
      Mechanism Description
  • Increased risk of adverse reactions by the combination of Methylergometrine and Lorcaserin 

Recommended Action
      Management Lorcaserin should not be used in combination with serotonergic and dopaminergic drugs that are potent 5-HT2B receptor agonists and are known to increase the risk of cardiac valvulopathy (e.g., cabergoline, pergolide, ergot alkaloids). Patients who develop signs and symptoms of valvular heart disease such as dizziness, fatigue, weakness, dyspnea, edema, or arrhythmia during treatment with lorcaserin should seek prompt medical attention. Discontinuation of lorcaserin should be considered.

References
1 Product Information. Belviq (lorcaserin). Eisai Inc, Teaneck, NJ.
2 Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
3 Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL "Evidence for possible involvement of 5-HT2B receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications." Circulation 102 (2000): 2836-41.[PMID: 11104741]