Drug General Information (ID: DDIHL0AYV3)
  Drug Name Selegiline Drug Info Trimethaphan Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Dopaminergic Antiparkinsonism Agents/Mao Inhibitors Antihypertensive Agents
  Structure

 Mechanism of Selegiline-Trimethaphan Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Selegiline Trimethaphan
      Mechanism Hypotensive effects
Monoamine oxidase non-selective  Inhibitor
Hypotensive effects
Neuronal acetylcholine receptor alpha-4  Antagonist
      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).
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      Key Mechanism Factor 2
Factor Name Neuronal acetylcholine receptor alpha-4
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Structure Sequence
MELGGPGAPRLLPPLLLLLGTGLLRASSHVETRAHAEERLLKKLFSGYNKWSRPVANISDVVLVRFGLSIAQLIDVDEKNQMMTTNVWVKQEWHDYKLRWDPADYENVTSIRIPSELIWRPDIVLYNNADGDFAVTHLTKAHLFHDGRVQWTPPAIYKSSCSIDVTFFPFDQQNCTMKFGSWTYDKAKIDLVNMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFVIRRLPLFYTINLIIPCLLISCLTVLVFYLPSECGEKITLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRSPRTHTMPTWVRRVFLDIVPRLLLMKRPSVVKDNCRRLIESMHKMASAPRFWPEPEGEPPATSGTQSLHPPSPSFCVPLDVPAEPGPSCKSPSDQLPPQQPLEAEKASPHPSPGPCRPPHGTQAPGLAKARSLSVQHMSSPGEAVEGGVRCRSRSIQYCVPRDDAAPEADGQAAGALASRNTHSAELPPPDQPSPCKCTCKKEPSSVSPSATVKTRSTKAPPPHLPLSPALTRAVEGVQYIADHLKAEDTDFSVKEDWKYVAMVIDRIFLWMFIIVCLLGTVGLFLPPWLAGMI
Gene Name CHRNA4
Uniprot ID ACHA4_HUMAN
KEGG Pathway hsa:1137
Protein Family Ligand-gated ion channel (TC 1.A.9) family
Protein Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Selegiline and Trimethaphan 

Recommended Action
      Management Caution is advised during coadministration of MAOIs and other medications with hypotensive effects, especially during the first few weeks of treatment. Close monitoring for development of hypotension is recommended. Ambulatory patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References
1 Product Information. Marplan (isocarboxazid) Roche Laboratories, Nutley, NJ.
2 Reggev A, Vollhardt BR "Bradycardia induced by an interaction between phenelzine and beta blockers." Psychosomatics 30 (1992): 106-8. [PMID: 2913594]
3 Schulz R, Antonin KH, Hoffmann E, et al "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36. [PMID: 2510962]