Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIXHSCZR8)
  Drug Name Meperidine Drug Info Safinamide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anesthetics Dopaminergic Antiparkinsonism Agents
  Structure

 Mechanism of Meperidine-Safinamide Interaction (Severity Level: Major)
     Additive serotonergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Meperidine Safinamide
      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 Meperidine and Safinamide 

Recommended Action
      Management Because the interaction may involve a class-effect of MAOIs, concomitant administration of the selective MAO-B inhibitor, safinamide, with certain opioids such as meperidine, methadone, propoxyphene, and tramadol is considered contraindicated. Some authorities suggest that at least 7 to 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with opioids. Although morphine may also have significant CNS interactions with MAOIs, it is generally considered a safer alternative in patients treated with MAOIs who require a narcotic analgesic. A sensitivity test should be performed in which repeated, small, incremental doses of morphine are administered over the course of several hours while overall clinical status and vital signs are carefully monitored.

References
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20 Product Information. Actiq (fentanyl). Abbott Pharmaceutical, Abbott Park, IL.
21 Product Information. Azilect (rasagiline). Teva Pharmaceuticals USA, North Wales, PA.
22 Product Information. Demerol (meperidine). Sanofi Winthrop Pharmaceuticals, New York, NY.
23 Product Information. Duragesic Transdermal System (fentanyl). Janssen Pharmaceutica, Titusville, NJ.
24 Product Information. Eldepryl (selegiline). Somerset Pharmaceuticals Inc, Tampa, FL.
25 Product Information. Furoxone (furazolidone). Roberts Pharmaceutical Corporation, Eatontown, NJ.
26 Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
27 Product Information. Matulane (procarbazine). Roche Laboratories, Nutley, NJ.
28 Product Information. Meperidine Hydrochloride Injection, USP (meperidine) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
29 Product Information. Methylene Blue (methylene blue). American Regent Laboratories Inc, Shirley, NY.
30 Product Information. Nardil (phenelzine). Parke-Dvis, Morris Plains, NJ.
31 Product Information. Parnate (tranylcypromine). SmithKline Beecham, Philadelphia, PA.
32 Product Information. Xadago (safinamide). US WorldMeds LLC, Louisville , KY.
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