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. 2023 Dec 1;33(9):207-216.
doi: 10.1097/FPC.0000000000000509. Epub 2023 Sep 20.

PharmGKB summary: disulfiram pathway

Aneysis D Gonzalez-Suarez  1 , Caroline F Thorn  2 , Michelle Whirl-Carrillo  2 , Teri E Klein  2   3
Affiliations

PharmGKB summary: disulfiram pathway

Aneysis D Gonzalez-Suarez et al. Pharmacogenet Genomics. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: None.

Figures

Fig. 1:
Fig. 1:
Metabolism of disulfiram by candidate genes in the stomach, liver, and plasma. Illustration of the metabolic pathways of disulfiram mediated by candidate genes in the stomach, liver, and plasma. The diagram highlights the various metabolites produced during disulfiram’s metabolism. AdoHcy, S-Adenosyl-L-Homocysteine; AdoMet, S-Adenosyl-L-Methionine; CYP2E1, Cytochrome P450 Family 2 Subfamily E Member 1; DDC, diethyldithiocarbamic acid; GSR, glutathione-disulfide reductase; TPMT, thiopurine S-methyltransferase (online: https://www.pharmgkb.org/pathway/PA166287601).
Fig. 2:
Fig. 2:
Pharmacodynamics of disulfiram on ethanol and cocaine metabolism. Illustration of disulfiram’s interactions in the pharmacokinetics of ethanol and cocaine. Disulfiram inhibits aldehyde dehydrogenase enzymes involved in ethanol metabolism, along with multiple enzymes in the metabolism of cocaine. ADH1B, Alcohol Dehydrogenase 1B (Class I); ADH4, Alcohol Dehydrogenase 4 (Class II); ALDH2, Aldehyde Dehydrogenase 2 Family Member; BCHE, butyrylcholinesterase; CES1/CES2, Carboxylesterase ½; CYP3A4, Cytochrome P450 Family 3 Subfamily A Member 4; SLC6A3/SLC6A4, SLC6A5, Solute Carrier Family 6 Member 3/4/5 (online: https://www.pharmgkb.org/pathway/PA166287721).
Fig. 3:
Fig. 3:
Pharmacodynamic effects of disulfiram on dopaminergic neurons. Stylized diagram showing candidate genes involved in the pharmacodynamic effects of disulfiram on a dopaminergic neuron. Disulfiram exerts its effects on dopaminergic neurons by targeting different isoforms of aldehyde dehydrogenase, at multiple stages of dopamine’s metabolism. ALDH1A1, Aldehyde Dehydrogenase 1 Family Member A1; ALDH2, Aldehyde Dehydrogenase 2 Family Member; COMT, Catechol-O-Methyltransferase; DDC, Dopa Decarboxylase; MAOA/MAOB, Monoamine Oxidase A/B; TH, Tyrosine Hydroxylase (online: https://www.pharmgkb.org/pathway/PA166287741).
Fig. 4:
Fig. 4:
Pharmacodynamic effects of disulfiram on serotonergic neurons. Stylized diagram showing candidate genes involved in the pharmacodynamic effects of disulfiram on a serotonergic neuron. Disulfiram inhibits two isoforms of aldehyde dehydrogenase and tryptophan h 338 hydroxylase. ALDH1A1, Aldehyde Dehydrogenase 1 Family Member A1; ALDH2, Aldehyde Dehydrogenase 2 Family Member; DDC, Dopa Decarboxylase; MAOA/MAOB, Monoamine Oxidase A/B; SULT1A1, Sulfotransferase Family 1A Member 1; TPH2, Tryptophan Hydroxylase 2; UGT1A6, UDP Glucuronosyltransferase 1 Family Polypeptide A6 (online: https://www.pharmgkb.org/pathway/PA166287781).
Fig. 5:
Fig. 5:
Candidate genes involved in a sympathetic neuroeffector junction. Stylized diagram of the candidate genes in a noradrenergic-myocyte synaptic junction. ADM, Adrenomedullin; ADRA1/ADRA2, Adrenoceptor Alpha 1A/1B; ADRB1/ADRB2, Adrenoceptor Beta 1/2; CHGA, Chromogranin A; DBH, Dopamine Beta-Hydroxylase; GPR182, G Protein-Coupled Receptor 182; NPY, Neuropeptide Y; NPY1R/NPY2R, Neuropeptide Y Receptor Y1/Y2; SLC18A1/SLC18A2, Solute Carrier Family 18 Member A1/A2; SLC18A2, Solute Carrier Family 18 Member A2; SLC22A3, Solute Carrier Family 22 Member 3; SLC6A2, Solute Carrier Family 6 Member 2 (online: https://www.pharmgkb.org/pathway/PA2042)
See this image and copyright information in PMC

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