About this pathway
Disulfiram inhibits ALDH in the metabolism of serotonin by serotonergic neurons. Here, serotonin (5-hydroxytryptamine, 5-HT) is converted into 5-hydroxyindole-3-acetaldehyde (5-hydroxyindole-3-aldehyde, 5-HIAL). 5-HIAL can be further metabolized by ALDH, which produces 5-hydroxyindole-3-acetic acid (5- HIAA), or by ADH and aldehyde reductase (ALDRL2/5), resulting in 5-hydroxytryptophol (5-HTOL). This change in the 5-HTOL/5-HIAA is thought to contribute to the cessation of cocaine use in patients [Article:9514292]. In addition to serotonin’s metabolism. disulfiram also impacts its synthesis. It does this by inhibiting tyrosine hydroxylase, primarily isoform 2 (TPH 2) [Article:2474765]. 5-HT is synthesized by the conversion of L-tryptophan into L-5-hydroxytryptophan (5-HTP) by TPH, which is further decarboxylated by AADC. By inhibiting the synthesis of serotonin—a neurotransmitter thought to heighten the effects of cocaine—disulfiram may be compromising the euphoric effects of cocaine.
Reactions & interactions (19)
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Biochemical Reaction
5-hydroxyindole-3-acetaldehyde → 5-hydroxyindole-3-acetic acid
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Biochemical Reaction
5-hydroxytryptophol → 5-hydroxytryptophol sulfate
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Biochemical Reaction
serotonin → 5-hydroxyindole-3-acetaldehyde
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Biochemical Reaction
5-hydroxyindole-3-acetaldehyde → 5-hydroxytryptophol
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Biochemical Reaction
l-tryptophan → 5-hydroxy-L-tryptophan
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Biochemical Reaction
5-hydroxytryptophol → 5-hydroxytryptophol glucuronide
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Biochemical Reaction
5-hydroxy-L-tryptophan → serotonin
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Catalysis
ALDH2 → Biochemical Reaction
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Catalysis
ALDH1A1 → Biochemical Reaction
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Catalysis
SULT1A1 → Biochemical Reaction
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Catalysis
MAOA → Biochemical Reaction
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Catalysis
MAOB → Biochemical Reaction
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Catalysis
ADH1B → Biochemical Reaction
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Catalysis
TPH2 → Biochemical Reaction
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Catalysis
UGT1A6 → Biochemical Reaction
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Catalysis
DDC → Biochemical Reaction
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Inhibition
disulfiram → ALDH2
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Inhibition
disulfiram → TPH2
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Inhibition
disulfiram → ALDH1A1
Edit history (5)
- 2023-02-01 Create
- 2023-07-21 Update Updated text and links.
- 2023-09-22 Update Added citation
- 2023-09-25 Update Added related pathways
- 2024-09-04 Update fixed typo