Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI0BMP1DQ)
  Drug Name Clonidine Drug Info Clomipramine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Antidepressants
  Structure

 Mechanism of Clonidine-Clomipramine Interaction (Severity Level: Major)
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Clonidine Clomipramine
      Mechanism Antihypertensive agent
Alpha-2 adrenergic receptor  Agonist 		Antihypertensive agent
Noradrenaline transporter  Inducer
      Key Mechanism Factor 1
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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      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 Clonidine when combined with Clomipramine 

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]