Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIB6WLQHT)
  Drug Name Imipramine Drug Info Methoxamine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antihypertensive Agents
  Structure

 Mechanism of Imipramine-Methoxamine Interaction (Severity Level: Major)
     Additive hypertensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Imipramine Methoxamine
      Mechanism Hypertensive effects
Norepinephrine transporter  Inhibitor 		Hypertensive effects
Alpha-1 adrenergic receptor  Agonist
      Key Mechanism Factor 1
Factor Name Sodium-dependent noradrenaline transporter
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Structure Sequence
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWGKKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYNREGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTWNSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLCLMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFYRLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFAIFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSSMGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTSILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINFKPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHLVAQRDIRQFQLQHWLAI
Gene Name SLC6A2
Uniprot ID SC6A2_HUMAN
KEGG Pathway hsa:6530
Protein Family Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family, SLC6A2 subfamily
Protein Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
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      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 Imipramine and Methoxamine 

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]