Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIEK2ZAIW)
  Drug Name Tranylcypromine Drug Info Guanethidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antihypertensive Agents
  Structure

 Mechanism of Tranylcypromine-Guanethidine Interaction (Severity Level: Moderate)
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tranylcypromine Guanethidine
      Mechanism Hypertensive effects
Monoamine oxidase non-selective  Inhibitor 		Antihypertensive agent
Noradrenaline transporter  Inducer
      Key Mechanism Factor 1
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).
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      Key Mechanism Factor 2
Factor Name Norepinephrine 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
Protein Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
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      Mechanism Description
  • Antagonize the effect of Guanethidine when combined with Tranylcypromine 

Recommended Action
      Management While clinical data are lacking, guanadrel and guanethidine should preferably not be used with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, linezolid, methylene blue, procarbazine). The manufacturer of phenelzine considers the combination contraindicated. At least 7 to 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with guanadrel or guanethidine. If they have been used together, clinicians should be aware that significant hypotension may occur following withdrawal of MAOI therapy.

References
1 Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31. [PMID: 8845455]
2 Iversen LL "Inhibition of noradrenaline uptake by drugs." J Pharm Pharmacol 17 (1965): 62-4. [PMID: 14285701]
3 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]