Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIEFN652Z)
  Drug Name Doxepin (topical) Drug Info Guanethidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antihypertensive Agents
  Structure

 Mechanism of Doxepin (topical)-Guanethidine Interaction (Severity Level: Moderate)
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Doxepin (topical) Guanethidine
      Mechanism Hypertensive effects Antihypertensive agent
Noradrenaline transporter  Inhibitor
      Key Mechanism Factor 1
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 Doxepin (topical) when combined with Guanethidine 

Recommended Action
      Management Either a different antidepressant or a different antihypertensive agent (such as an ACE inhibitor or beta-blocker) should be considered. If patients do receive this combination, their blood pressure should be closely monitored when initiating or discontinuing either drug.

References
1 Stone CA, Porter CC, Stavorski JM, et al "Antagonism of certain effects of catecholamine-depleting agents by antidepressant and related drugs." J Pharmacol Exp Ther 144 (1964): 196-204
2 Gokhale SD, Gulati OD, Udwadia BP "Antagonism of the adrenergic neurone blocking action of guanethidine by certain antidepressant and antihistamine drugs." Arch Int Pharmacodyn Ther 160 (1966): 321-9
3 Koe BK, Constantine JW "Blocking H 3 -norepinephrine uptake and some guanethidine-induced effects with tricyclic psychotherapeutic drugs." Arch Int Pharmacodyn Ther 195 (1972): 71-80