Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIT8E9ZMR)
  Drug Name Selegiline Drug Info Tapentadol Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Dopaminergic Antiparkinsonism Agents/Mao Inhibitors Narcotic Analgesics
  Structure

 Mechanism of Selegiline-Tapentadol Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Selegiline Tapentadol
      Mechanism 1 Serotonergic effects
Monoamine oxidase non-selective  Inhibitor 		Serotonergic effects
Serotonin transporter  Inhibitor
      Key Mechanism Factor 1
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).
    Click to Show/Hide
      Key Mechanism Factor 2
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.
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      Mechanism Description
  • Additive serotonergic effects by the combination of Selegiline and Tapentadol 
     Increased risk of lowers seizure threshold Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Selegiline Tapentadol
      Mechanism 2 Lower seizure threshold Lower seizure threshold
      Key Mechanism Factor 3
Factor Name Lowers seizure threshold
Factor Description The combination of medications that lower the seizure threshold is a factor that makes people with epilepsy more likely to have seizures. A seizure is a sudden, uncontrolled electrical disturbance in the brain that can cause changes in your behavior, movements or sensations, and level of consciousness.
      Mechanism Description
  • Increased risk of lowers seizure threshold by the combination of Selegiline and Tapentadol 

Recommended Action
      Management The use of tapentadol in patients currently receiving or within 14 days of receiving a monoamine oxidase inhibitor (MAOI) is considered contraindicated.

References
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2 Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2. [PMID: 7476638]
3 Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31. [PMID: 8845455]
4 De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5. [PMID: 4379192]
5 Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2. [PMID: 8748434]
6 Gillman PK "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth (2005):. [PMID: 16051647]
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8 Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763. [PMID: 9330840]
9 Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8. [PMID: 8257462]
10 Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7. [PMID: 5655478]
11 Product Information. Nucynta (tapentadol). PriCara Pharmaceuticals, Raritan, NJ.
12 Staufenberg EF, Tantam D "Malignant hyperpyrexia syndrome in combined treatment." Br J Psychiatry 154 (1989): 577-8. [PMID: 2590798]
13 Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13. [PMID: 2035713]