Therapeutic Results and Clinical Manifestations Following the Use of Tetraethylthiuram Disulfide (Antabuse)

Child, George P.; Osinski, Walter A.; Bennett, Robert E.; Davidoff, Eugene

doi:10.1176/ajp.107.10.774

Cited by 20 publications

(3 citation statements)

References 6 publications

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“…Reports on disulfiram neuropathy date back at least half a century (15) and data on the clinical signs and morphology are available from both human cases and animal studies. Although the nature of some lesions remains controversial, a number of generally accepted characteristics have been established for disulfiram toxicity.…”

Section: Disulfiram (Bis(diethylthiocarbamoyl)disulfide or Antabusementioning

confidence: 99%

Disulfiram Produces a Non-Carbon Disulfide-Dependent Schwannopathy in the Rat

Tonkin¹,

Erve²,

Valentine³

2000

J Neuropathol Exp Neurol

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Abstract. Disulfiram is a dithiocarbamate drug used for alcohol aversion therapy that produces a distal sensorimotor peripheral neuropathy in certain individuals. Because carbon disulfide, a disulfiram metabolite, produces a peripheral neuropathy clinically similar to disulfiram, it has been postulated that disulfiram neuropathy results from CS 2 release in vivo. The current study evaluated the morphological changes produced by disulfiram and the contribution of CS 2 -mediated protein cross-linking to disulfiram-induced neuropathy. Male Sprague-Dawley rats were administered 1% w/w disulfiram in their feed for 2, 4, 5, or 7 wk, and erythrocyte spectrin, hemoglobin, and neurofilament preparations were isolated and the extent of cross-linking assessed by SDS-PAGE, RP-HPLC, and Western blotting, respectively. Spinal cord and peripheral nerve sections were obtained from separate treated animals and assessed by light and electron microscopy. Significant protein cross-linking was only detected in neurofilament preparations obtained after 7 wk of exposure. Morphological changes were observed after 4 wk exposure and consisted of vacuoles within the Schwann cell cytoplasm and segmental demyelination. No neurofilamentous axonal swellings were detected and no significant changes were observed in the CNS. Because disulfiram neuropathy lacks both the morphological changes and intermolecular cross-linking characteristic of CS 2 , we conclude that disulfiram neuropathy is not mediated by the axonal toxicant CS 2 ; instead, disulfiram appears to be a primary Schwann cell toxicant. Recognition of a diethylcarbamoyl adduct on globin and axonal proteins presents a novel putative neurotoxic mechanism for disulfiram.

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Section: Disulfiram (Bis(diethylthiocarbamoyl)disulfide or Antabusementioning

confidence: 99%

Disulfiram Produces a Non-Carbon Disulfide-Dependent Schwannopathy in the Rat

Tonkin¹,

Erve²,

Valentine³

2000

J Neuropathol Exp Neurol

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“…Hayman and Wilkins (1956) reported six instances of this condition arising in patients taking disulfiram, 250 to 750 mg., with vitamin-B preparations for 4 to 12 months; another patient developed peripheral neuropathy after a severe alcohol-disulfiram reaction. All the cases described in the literature had received such reactions, but only the three cases of Child et al (1951) and the seventh case of Hayman and Wilkins (1956) developed neuropathy in close relation to the reaction. No alcohol was consumed by our patient, and the reason for the rapid onset after premonitory symptoms for two weeks is not clear.…”

Section: Noctementioning

confidence: 99%

“…Chloral has been included among the causes of polyneuropathy (Stewart, 1925 ;Harris, 1926), though we have been unable to find a case report. Child et al (1951) reported three cases of " questionable peripheral neuritis" in 120 patients receiving disulfiram. All three had received the drug within four days of an alcoholic bout.…”

Section: Noctementioning

confidence: 99%