Disulfiram Implantation Critically Evaluated

Malcolm, M. T.; Madden, J. S.; Williams, Aparna

doi:10.1192/bjp.125.5.485

Cited by 47 publications

(6 citation statements)

References 5 publications

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“…Disulfiram is often administered therapeutically as a subcutaneous implant. The efficacy of this procedure is doubtful, owing to the low watersolubility of the compound and its consequent negligible steady-state concentration in vivo after implantation (Malcolm et al, 1974). In this respect, the physiological properties of some of the aldehyde dehydrogenase inhibitors used in the present study may warrant examination.…”

Section: Methodsmentioning

confidence: 95%

The effect of some analogues of disulfiram on the aldehyde dehydrogenases of sheep liver

Tm¹

1976

Biochemical Journal

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The effect of some close structural analogues of disulfiram on the activity of the cytoplasmic and mitochondrial aldehyde dehydrogenases of sheep liver was studied. Several thiuram disulphides are equally potent inhibitors of the cytoplasmic enzyme, but in all cases the mitochondrial enzyme is much less strongly affected. Tetramethylthiuram monosulphide decreases the activity of the cytoplasmic enzyme in a process apparently involving a covalent interaction.

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Section: Methodsmentioning

confidence: 95%

The effect of some analogues of disulfiram on the aldehyde dehydrogenases of sheep liver

Tm¹

1976

Biochemical Journal

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“…Swinson 1970 reported a case when itching and pain at the site of implant followed an ADR, in a man who had previously remained abstinent for six months. He commented on this unexpected finding, and suggested it might be evidence for tlie continuing eflect of Disulfiram over a period of time, a suggestion since refuted by biochemical studies of blood Disulfiram levels (Malcolm et al, 1974).…”

Section: Discussionmentioning

confidence: 98%

An Allergic Reaction to Disulfiram Implant

Black¹

1979

British Journal of Addiction to Alcohol & Other Drugs

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“…In an attempt of measuring disulfiram in blood, Brown et al reported that 12 h after a single 200-mg dose, the blood level of the drug was approximately 4.5 mg/liter (33). Moreover, after oral administration of the daily dose of 200 mg for 14 days, the blood level of disulfiram increased to 8.3 mg/liter (34,35). Since the recommended daily dose of disulfiram could be optimized to 500 mg (36), it is possible that the blood concentration of the drug can reach a level that potentially inhibits the susceptible organisms (i.e., P. insidiosum) that have an MIC 50 of Ͼ8 mg/liter.…”

Section: Discussionmentioning

confidence: 99%

The Repurposed Drug Disulfiram Inhibits Urease and Aldehyde Dehydrogenase and Prevents In Vitro Growth of the Oomycete Pythium insidiosum

Krajaejun

Lohnoo

Yingyong

et al. 2019

Antimicrob Agents Chemother

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Pythium insidiosum is an oomycete microorganism that causes a lifethreatening infectious disease, called pythiosis, in humans and animals. The disease has been increasingly reported worldwide. Conventional antifungal drugs are ineffective against P. insidiosum. Treatment of pythiosis requires the extensive removal of infected tissue (i.e., eye and leg), but inadequate surgery and recurrent infection often occur. A more effective treatment is needed for pythiosis patients. Drug repurposing is a promising strategy for the identification of a U.S. Food and Drug Administration-approved drug for the control of P. insidiosum. Disulfiram has been approved to treat alcoholism, but it exhibits antimicrobial activity against various pathogens. In this study, we explored whether disulfiram possesses an anti-P. insidiosum activity. A total of 27 P. insidiosum strains, isolated from various hosts and geographic areas, were susceptible to disulfiram in a dose-dependent manner. The MIC range of disulfiram against P. insidiosum (8 to 32 mg/liter) was in line with that of other pathogens. Proteogenomic analysis indicated that several potential targets of disulfiram (i.e., aldehyde dehydrogenase and urease) were present in P. insidiosum. By homology modeling and molecular docking, disulfiram can bind the putative aldehyde dehydrogenase and urease of P. insidiosum at low energies (i.e., -6.1 and -4.0 Kcal/mol, respectively). Disulfiram diminished the biochemical activities of these enzymes. In conclusion, disulfiram can inhibit the growth of many pathogenic microorganisms, including P. insidiosum. The drug can bind and inactivate multiple proteins of P. insidiosum, which may contribute to its broad antimicrobial property. Drug repurposing of disulfiram could be a new treatment option for pythiosis.

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Disulfiram Implantation Critically Evaluated

Cited by 47 publications

References 5 publications

The effect of some analogues of disulfiram on the aldehyde dehydrogenases of sheep liver

The effect of some analogues of disulfiram on the aldehyde dehydrogenases of sheep liver

An Allergic Reaction to Disulfiram Implant

The Repurposed Drug Disulfiram Inhibits Urease and Aldehyde Dehydrogenase and Prevents In Vitro Growth of the Oomycete Pythium insidiosum

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