Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIZK9Y7HC)
Drug Name			Norepinephrine		Drug Info		Clomipramine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Vasoconstrictor Agents				Antidepressants
Structure

Mechanism of Norepinephrine-Clomipramine Interaction (Severity Level: Major)
Additive hypertensive effects Click to Show/Hide Mechanism Graph

Drug Name		Norepinephrine				Clomipramine
Mechanism		Hypertensive effects Beta-1 adrenergic receptor Agonist				Hypertensive effects Norepinephrine transporter Inhibitor
Key Mechanism Factor 1
		Factor Name		Adrenergic receptor beta-1				× Structure Sequence MGAGVLVLGASEPGNLSSAAPLPDGAATAARLLVPASPPASLLPPASESPEPLSQQWTAGMGLLMALIVLLIVAGNVLVIVAIAKTPRLQTLTNLFIMSLASADLVMGLLVVPFGATIVVWGRWEYGSFFCELWTSVDVLCVTASIETLCVIALDRYLAITSPFRYQSLLTRARARGLVCTVWAISALVSFLPILMHWWRAESDEARRCYNDPKCCDFVTNRAYAIASSVVSFYVPLCIMAFVYLRVFREAQKQVKKIDSCERRFLGGPARPPSPSPSPVPAPAPPPGPPRPAAAAATAPLANGRAGKRRPSRLVALREQKALKTLGIIMGVFTLCWLPFFLANVVKAFHRELVPDRLFVFFNWLGYANSAFNPIIYCRSPDFRKAFQRLLCCARRAARRRHATHGDRPRASGCLARPGPPPSPGAASDDDDDDVVGATPPARLLEPWAGCNGGAAADSDSSLDEPCRPGFASESKV
		Gene Name		ADRB1
		Uniprot ID		ADRB1_HUMAN
		KEGG Pathway		hsa:153
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062). Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Sodium-dependent noradrenaline transporter				× 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. Click to Show/Hide
Mechanism Description		Additive hypertensive effects by the combination of Norepinephrine and Clomipramine

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]