Drug General Information (ID: DDI64EVGZ7)
  Drug Name Disulfiram Drug Info Benznidazole Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Alcohol Deterrents Trypanocidal Agents
  Structure

 Mechanism of Disulfiram-Benznidazole Interaction (Severity Level: Major)
     Increased risk of other adverse reactions (Unspecific) Click to Show/Hide Mechanism Graph
      Drug Name Disulfiram Benznidazole
      Mechanism Disulfiram-like reaction
Aldehyde dehydrogenase  Inhibitor
Disulfiram-like reaction
Aldehyde dehydrogenase  Inhibitor
      Key Mechanism Factor 1
Factor Name Aldehyde dehydrogenase 1
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Structure Sequence
MSSSGTPDLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKEDVDKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMESMNGGKLYSNAYLNDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHEPIGVCGQIIPWNFPLVMLIWKIGPALSCGNTVVVKPAEQTPLTALHVASLIKEAGFPPGVVNIVPGYGPTAGAAISSHMDIDKVAFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQGQCCIAASRIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDLIESGKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSLDDVIKRANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYGVVSAQCPFGGFKMSGNGRELGEYGFHEYTEVKTVTVKISQKNS
Gene Name ALDH1A1
Uniprot ID AL1A1_HUMAN
KEGG Pathway hsa:216
Protein Family Aldehyde dehydrogenase family
Protein Function
Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:19296407, PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:26373694, PubMed:25450233). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:19296407, PubMed:12941160, PubMed:15623782). Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Increased risk of adverse reactions by the combination of Disulfiram and Benznidazole 

Recommended Action
      Management Nitroimidazole therapy should not be administered with disulfiram. Metronidazole and benznidazole are specifically contraindicated in patients who have taken disulfiram within the last two weeks according to their product labeling.

References
1 Product Information. Metrogel-Vaginal (metronidazole). Curatek Pharmaceuticals Ltd, Elk Grove Village, IL.
2 Knee ST, Razani J "Acute organic brain syndrome: a complication of disulfiram therapy." Am J Psychiatry 131 (1974): 1281-2.[PMID: 4419107]
3 Scher JM "Psychotic reaction to disulfiram." JAMA 201 (1967): 175.[PMID: 6072487]