Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIBE32RUF)
  Drug Name Metyrosine Drug Info Amifostine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Cytoprotective Agent
  Structure

 Mechanism of Metyrosine-Amifostine Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Metyrosine Amifostine
      Mechanism 1 Antihypertensive agent
Tyrosine 3-monooxygenase  Binder 		Antihypertensive agent
      Key Mechanism Factor 1
Factor Name Tyrosine 3-monooxygenase
×
Structure Sequence
MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTPRSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPRATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVRQVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEIAFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNIPQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYGAGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYASRIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
Gene Name TH
Uniprot ID TY3H_HUMAN
KEGG Pathway hsa:7054
Protein Family Biopterin-dependent aromatic amino acid hydroxylase family
Protein Function
Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of cathecolamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (PubMed:17391063, PubMed:1680128, PubMed:15287903, PubMed:8528210, Ref.18, PubMed:34922205, PubMed:24753243). In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity). Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Metyrosine and Amifostine 
      Mechanism 2 Antihypertensive agent
Tyrosine 3-monooxygenase  Binder 		Hypotensive effects
      Key Mechanism Factor 2
Factor Name Tyrosine 3-monooxygenase
×
Structure Sequence
MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTPRSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPRATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVRQVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEIAFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNIPQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCCHELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYGAGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYASRIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG
Gene Name TH
Uniprot ID TY3H_HUMAN
KEGG Pathway hsa:7054
Protein Family Biopterin-dependent aromatic amino acid hydroxylase family
Protein Function
Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of cathecolamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (PubMed:17391063, PubMed:1680128, PubMed:15287903, PubMed:8528210, Ref.18, PubMed:34922205, PubMed:24753243). In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity). Positively regulates the regression of retinal hyaloid vessels during postnatal development (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Metyrosine and Amifostine 

Recommended Action
      Management If medically feasible, antihypertensive medications should be interrupted 24 hours prior to amifostine administration. Blood pressure should be closely monitored during and after treatment. In addition to hypotension, transient hypertension or exacerbation of preexisting hypertension may occur from intravenous hydration, discontinuation of antihypertensive medications, or other causes. Patients who continue their hypotensive medication(s) during amifostine therapy should be carefully monitored for the development of hypotension.

References
1 Bailey DG, Dresser GK "Natural products and adverse drug interactions." Can Med Assoc J 170 (2004): 1531-2. [PMID: 15136542]
2 Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc, Markham, ON.
3 Product Information. Ethyol (amifostine). Alza, Palo Alto, CA.