Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIMN8OXUL)
  Drug Name Nortriptyline Drug Info Clonidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antihypertensive Agents
  Structure

 Mechanism of Nortriptyline-Clonidine Interaction (Severity Level: Major)
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Nortriptyline Clonidine
      Mechanism Hypertensive effects
Noradrenaline transporter  Inhibitor 		Antihypertensive agent
Alpha-2 adrenergic receptor  Agonist
      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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      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-2 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
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      Mechanism Description
  • Antagonize the effect of Clonidine when combined with Nortriptyline 

Recommended Action
      Management It is recommended that this combination be avoided. If no alternatives exist and this combination must be used, blood pressure should be monitored closely, especially during the first few weeks of therapy. When clonidine, the TCA, or the combination is discontinued, gradual withdrawal is recommended to prevent abrupt blood pressure fluctuations. Patients should be advised to seek medical help if they develop potential symptoms of a hypertensive crisis such as nausea, vomiting, sweating, flushing, dizziness, stiff neck, headache or palpitations.

References
1 Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990):.
2 Stiff JL, Harris DB "Clonidine withdrawal complicated by amitriptyline therapy." Anesthesiology 59 (1983): 73-4.[PMID: 6859615]
3 Elliott HL, McLean K, Sumner DJ, Reid JL "Absence of an effect of mianserin on the actions of clonidine or methyldopa in hypertensive patients." Eur J Clin Pharmacol 24 (1983): 15-9.[PMID: 6299752]