Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI7LBAF4Q)
  Drug Name Tramadol Drug Info Safinamide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Dopaminergic Antiparkinsonism Agents
  Structure

 Mechanism of Tramadol-Safinamide Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tramadol Safinamide
      Mechanism 1 Serotonergic effects
Serotonin transporter  Inhibitor 		Serotonergic effects
Monoamine oxidase-B 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 type B
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Structure Sequence
MSNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYVGPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRTMDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVSALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQTRENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYYKEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERLKKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRIYFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTFLERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
Gene Name MAOB
Uniprot ID AOFB_HUMAN
KEGG Pathway hsa:4129
Protein Family Flavin monoamine oxidase family
Protein Function
Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079). Preferentially degrades benzylamine and phenylethylamine (PubMed:11134050, PubMed:8665924, PubMed:8316221, PubMed:11049757, PubMed:20493079).
    Click to Show/Hide
      Mechanism Description
  • Additive serotonergic effects by the combination of Tramadol and Safinamide 
     Increased risk of lowers seizure threshold Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tramadol Safinamide
      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 Tramadol and Safinamide 

Recommended Action
      Management Concurrent use of tramadol and MAOIs or other agents that possess MAOI activity (e.g., furazolidone, procarbazine) is considered contraindicated. At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with tramadol.

References
1 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]
2 Egberts AC, ter Borg J, Brodie-Meijer CC "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol 12 (1997): 181-2. [PMID: 9248876]
3 Gillman PK "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth (2005):. [PMID: 16051647]
4 Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6. [PMID: 8909274]
5 Mason BJ, Blackburn KH "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother 31 (1997): 175-7. [PMID: 9034418]
6 Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763. [PMID: 9330840]
7 Product Information. Eldepryl (selegiline). Somerset Pharmaceuticals Inc, Tampa, FL.
8 Product Information. Ultram (tramadol). McNeil Pharmaceutical, Raritan, NJ.
9 Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13. [PMID: 2035713]