Drug General Information (ID: DDIKWHCXR1)
  Drug Name Disulfiram Drug Info Sertraline Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Alcohol Deterrents Antidepressants
  Structure

 Mechanism of Disulfiram-Sertraline Interaction (Severity Level: Major)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Disulfiram Sertraline
      Mechanism Aldehyde dehydrogenase inhibitor Aldehyde dehydrogenase substrate
      Key Mechanism Factor 1
Factor Name Aldehyde dehydrogenase 1
×
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
  • Decreased metabolism of Sertraline caused by Disulfiram mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management The use of sertraline oral concentrate with disulfiram is considered contraindicated. A different formulation of sertraline or another selective serotonin reuptake inhibitor should be prescribed in patients receiving therapy with disulfiram.

References
1 Product Information. Antabuse (disulfiram). Wyeth-Ayerst Laboratories, Philadelphia, PA.
2 Product Information. Zoloft (sertraline). Roerig Division, New York, NY.