Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI2PT3WY8)
  Drug Name Nortriptyline Drug Info Epinephrine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Vasoconstrictor Agents
  Structure

 Mechanism of Nortriptyline-Epinephrine Interaction (Severity Level: Major)
     Additive hypertensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Nortriptyline Epinephrine
      Mechanism Hypertensive effects
Serotonin transporter  Inhibitor 		Hypertensive effects
Alpha-1 adrenergic receptor  Agonist
      Key Mechanism Factor 1
Factor Name Serotonin transporter
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Structure Sequence
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIMAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVTLTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV
Gene Name SLC6A4
Uniprot ID SC6A4_HUMAN
KEGG Pathway hsa:6532
Protein Family Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
Protein Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-1 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
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      Mechanism Description
  • Additive hypertensive effects by the combination of Nortriptyline and Epinephrine 

Recommended Action
      Management Parenteral administration of direct-acting sympathomimetic agents should preferably be avoided during therapy with tricyclic antidepressants except in cases of emergency (e.g., treatment of anaphylaxis). If concomitant use is necessary, initial dose and rate of administration of the sympathomimetic should be reduced, and cardiovascular status including blood pressure should be monitored closely. Although clinical data are lacking, it may be prudent to follow the same precaution with mixed-acting sympathomimetic agents.

References
1 Ghose K "Sympathomimetic amines and tricyclic antidepressant drugs." Neuropharmacology 19 (1980): 1251-4.[PMID: 7442960]
2 Borg KO, Johnsson G, Jordo L, Lundborg P, Ronn O, Welin-Fogelberg I "Interaction studies between three antidepressant drugs (zimelidine, imipramine and chlorimipramine) and noradrenaline in healthy volunteers and some pharmacokinetics of the drugs studied." Acta Pharmacol Toxicol (Copenh) 45 (1979): 198-205.[PMID: 506742]
3 Fritz H, Hagstam KE, Lindqvist B "Local skin necrosis after intravenous infusion of norepinephrine, and the concept of endotoxinaemia. A clinical study on 10 cases." Acta Med Scand 178 (1965): 403-16.[PMID: 5838313]