Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIXR1E7LF)
  Drug Name Citalopram Drug Info Rasagiline Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Antiparkinson Agents
  Structure

 Mechanism of Citalopram-Rasagiline Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Citalopram Rasagiline
      Mechanism Serotonergic effects
Serotonin transporter  Inhibitor 		Serotonergic effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 1
Factor Name Serotonin transporter
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Structure Sequence
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTRHSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLPYTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIMAWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIHRSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGATLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQDALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPASTFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVTLTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRICWVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIITPGTFKERIIKSITPETPTEIPCGDIRLNAV
Gene Name SLC6A4
Uniprot ID SC6A4_HUMAN
KEGG Pathway hsa:6532
Protein Family Sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family
Protein Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
    Click to Show/Hide
      Key Mechanism Factor 2
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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      Mechanism Description
  • Additive serotonergic effects by the combination of Citalopram and Rasagiline 

Recommended Action
      Management In general, SSRIs should not be used concurrently with MAOIs or other agents that possess MAOI activity. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with SSRIs, and vice versa. Due to the long half-life of fluoxetine and its active metabolite, norfluoxetine, a washout period of 5 weeks minimum is recommended when switching from fluoxetine to an MAOI. Similarly, a washout period of 3 weeks is recommended when switching from vortioxetine to an MAOI.

References
1 Beasley CM Jr, Masica DN, Heiligenstein JH, Wheadon DE, Zerbe RL "Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings." J Clin Psychopharmacol 13 (1993): 312-20. [PMID: 8227489]
2 Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5. [PMID: 9861909]
3 Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7. [PMID: 2198298]
4 Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50. [PMID: 1968472]
5 Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2. [PMID: 7476638]
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7 Feighner JP, Boyer WF, Tyler DL, Neborsky RJ "Adverse consequences of fluoxetine-MAOI combination therapy." J Clin Psychiatry 51 (1990): 222-5. [PMID: 2347858]
8 Graham PM, Ilett KF "Danger of MAOI therapy after fluoxetine withdrawal." Lancet 2 (1988): 1255-6. [PMID: 2903989]
9 Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6. [PMID: 8909274]
10 Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763. [PMID: 9330840]
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12 Product Information. Azilect (rasagiline). Teva Pharmaceuticals USA, North Wales, PA.
13 Ruiz F "Fluoxetine and the serotonin syndrome." Ann Emerg Med 24 (1994): 983-5. [PMID: 7978579]
14 Sternbach H "Danger of MAOI therapy after fluoxetine withdrawal." Lancet 2 (1988): 850-1. [PMID: 2902292]
15 Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13. [PMID: 2035713]
16 Suchowersky O, deVries J "Possible interactions between deprenyl and prozac." Can J Neurol Sci 17 (1990): 352-3. [PMID: 2119870]
17 Suchowersky O, deVries JD "Interaction of fluoxetine and selegiline." Can J Psychiatry 35 (1990): 571-2. [PMID: 2119876]