SEARCH · PubMed Health

Results for “Disulfiram”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed1977

Disulfiram toxicity and carbon disulfide poisoning.

The author compared the neurotoxic effects of disulfiram with those of carbon disulfide, a disulfiram metabolite. The results suggest that carbon disulfide is responsible for the behavioral and neurological side effects of disulfiram. If this is so, then some other toxic effects of carbon disulfide, including parkinsonism, choreoathetosis, and thalamic syndrome may follow the ingestion of more than 5 g of disulfiram by adults, and individuals receiving as little as 125 mg of disulfiram per day may be at a three- to four-fold greater risk for arteriosclerotic cardiovascular disease than a comparable population not receiving the drug.

Animals↗

PubMed1976

[Abstinence behavior and plasma concentration of disulfiram in alcoholics after esperal implantation].

Abstinence behaviour after disulfiram implantation has been investigated in 21 chronic alcoholics. The blood levels of disulfiram and its metabolites, carbon disulfide (CS2) and reduced disulfiram (diethyldithiocarbamate) were determined and the blood levels of patients with implants were compared with those of patients receiving disulfiram orally. The blood levels in the implanted patients were significantly lower than those of the group taking disulfiram orally. No metabolites were detectable after 3 months, despite the sensitive method employed. Nevertheless, 14 of the 21 chronic alcoholics remained abstinent for 6 months after implantation. This result is probably due in the main to psychotherapeutic guidance.

Adult↗

PubMed1976

Determination of disulfiram and its metabolites in human blood.

This work was initiated by the lack of a sensitive method for the determination of disulfiram and its metabolites in blood of patients treated with this drug. A method is described which allows the separate determination of carbon disulfide, free diethyldithiocarbamate and disulfides derived from disulfiram with adequate precision in 10 ml patient blood. It is based on a spectrophotometric determination of a yellow compound formed by trapping carbon disulfide produced from diethyldithiocarbamate and disulfiram in an ethanolic solution of diethylamine and copper(II)-acetate. Good quantitation of disulfiram and diethyldithiocarbamate in blood was achieved by trapping carbon disulfide produced when formic acid and cystein were added to the samples. During daily administration of 200 mg disulfiram to humans, concentrations of zero to 0.6 mug carbon disulfide and 0.2 to 1.0 mug diethyldithiocarbamate per ml blood were found using this method.

Carbon Disulfide↗

PubMed1976

[Digestive absorption, fixation and excretion of oral disulfiram in the rat].

Absorption, distribution and excretion of disulfiram and of one of its metabolites, diethyldithiocarbamate, were studied in rats orally treated with disulfiram (25 or 250 mg/kg). It was noted that this compound is absorbed in a proportion of 70-90 per cent of the administered dose but that diethyldithiocarbamate can appear already in the gut. After absorption, disulfiram and diethyldithiocarbamate impregnate specifically some tissues such as liver, kidney and muscle; blood and brain contain little or no disulfiram. The largest dose of disulfiram decreases fecal bolus and increases urinary volume favouring perhaps excretion of diethyldithiocarbamate.

Administration, Oral↗

PubMed1979

The effect of dietary disulfiram upon the tissue distribution and excretion of 14C-1,2-dibromoethane in the rat.

Dietary disulfiram enhances the toxicity of inhaled 1,2-dibromoethane in rats. This study was undertaken to determine whether the differential toxicity noted was associated with alterations in the levels of the compound and/or its metabolites in the target organs. A comparison of the levels of 14C in selected tissues of male rats, with and without dietary disulfiram, following the oral administration of 14C-1,2-dibromoethane was made. The results indicated that levels of radioactivity in the target organs of animals in the disulfiram group were significantly elevated both at 24 and 48 hours following compound administration. The data indicate a direct correlation between tissue levels and the enhancement of toxicity noted in the disulfiram-treated rats in the inhalation study. A significant elevation in the levels of radioactivity in washed liver nuclei obtained from animals receiving dietary disulfiram was also noted, suggesting a relationship between nuclear uptake and the increased incidence of liver tumors appearing in the disulfiran group in the inhalation study.

Animals↗

PubMed1979

Inhibition of N-n-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder cancer in rats by administration of disulfiram in the diet.

The objective of this study was to determine if disulfiram would influence the induction of urinary bladder cancer in rats given N-n-butyl-N(4-hydroxybuty)nitrosamine (BHBN). Adult male Wistar rats were divided into: Group 1, control diet, 30 rats; Group 2, control diet plus 0.025% BHBN in the drinking water, 60 rats; Group 3, control diet containing 0.5% disulfiram, 30 rats; and Group 4, control diet containing 0.5% disulfiram plus 0.025% BHBN in the drinking water, 60 rats. The animals were kept on these regimens for 15 weeks and then were transferred to and maintained on control diet. The average total intake of BHBN was 1.21 g/rat for Group 2 and 1.23 g/rat for Group 4. The cumulative incidences of bladder cancer at 25 weeks after initial exposure to BHBN were: Group 1, 0 of 9; Group 2, 27 of 27; Group 3, 0 of 9; and Group 4, 0 of 27. At termination of the experiment (32 to 42 weeks), the final bladder cancer incidences were: Group 1, 0 of 30 (0%); Group 2, 57 of 57 ()00%); Group 3, 0 of 24 (0%); and Group 4, 7 of 55 (13%). Except for a carcinoma of the renal pelvis in one rat in Group 2 and the bladder tumors in Groups 2 and 4, tumors were not detected in other organs of any of these rats. It was concluded that disulfiram significantly inhibited the induction of bladder cancer in rats exposed to BHBN. The mechanism of action of disulfiram in this process is under investigation.

Animals↗

PubMed1977

Cerebrospinal fluid homovanillic acid in male alcoholics: effects of disulfiram.

It is well know that if an individual maintained on disulfiram (Antabuse) ingests alcohol, excess acetaldehyde is formed, resulting in a toxic reaction. In addition to this toxic interaction with alcohol (the basis of its use as a deterrent), there are both behavioral and biochemical observations to suggest that disulfiram alone has a direct effect on the CNS. The possibility that some of disulfiram's effects are related to alterations in biogenic amine metabolism led to the present study of cerebrospinal fluid amine metabolites in a group of male alcoholics. In this group, disulfiram treatment was associated with a significant reduction in homovanillic acid, the major metabolite of dopamine, while no change was noted in 5-hydroxyindoleacetic acid, the major metabolite of serotonin. Prior to disulfiram, patients with withdrawal symptoms had significantly lower homovanillic acid than those without such symptoms.

Adult↗

PubMed1978

Catatonia associated with disulfiram therapy.

This is the first report of a catatonic syndrome occurring in a patient receiving disulfiram treatment. A causal relationship is strongly suggested by the mode of onset, the absence of a previous history of catatonia, and the rapid resolution of the syndrome within 72 hours of discontinuance of the disulfiram therapy. Neurophysiological mechanisms which aid in elucidating the role of disulfiram in the etiology of catatonia are discussed. It is important that physicians be alerted to this serious, potentially lethal, complication, as it is readily reversible if the disulfiram is discontinued and appropriate supportive measures are taken. Also, it appears that these patients may be more susceptible to complications with future disulfiram usage and should be strongly counseled to seek alternative therapies for their alcohol problems in the future.

Alcoholism↗

PubMed1979

Ethanol, disulfiram, and pyrazole: effects on interferon production in mice.

The effects of ethanol alone or combined with pyrazole or disulfiram were studied in reference to interferon production. Saline, ethanol (2 g/kg), pyrazole (2 mg/kg), or disulfiram (2 mg/kg) were injected, intraperitoneally, 3 hr after poly I:C, an interferon inducer. Drugs were administered either by a single injection, or twice daily for 7 days, and the mice were sacrificed 6 hr after poly I:C. Sera from mice were pooled, dialyzed, and assayed for interferon by the microplaque reduction method. Administration of ethanol alone reduced interferon production 76% and 66% after the single and the multiple injections, respectively. A similar inhibition of interferon occurred after either pyrazole or disulfiram, with a greater potency for pyrazole. Treatment with pyrazole prior to ethanol reduced interferon production further, but only after the 7-day schedule. All drugs tested affected cellular immunity as measured by interferon production. Moreover, reduced interferon production by these agents was associated with a loss of splenic lymphoid tissue, suggesting that ethanol, pyrazole, and disulfiram could affect susceptibility to viral infection.

Animals↗

PubMedDate not supplied

Disulfiram alters dopamine metabolism at sites in rat's forebrain as detected by push-pull perfusions.

The effect of tetraethylthiuramdisulfide (disulfiram) on the catabolism of dopamine within discrete regions of the brain was investigated in the unrestrained rat. After a guide cannula had been implanted stereotaxically, a given subcortical site was radiolabeled with 14C-dopamine (DA) by microinjecting 2.0 mu Ci in 2.0 microliters. Successive push-pull perfusates collected from each tissue were assayed by paper electrophoresis for the separation of DA metabolites. When disulfiram, a potent aldehyde dehydrogenase (ALDH) inhibitor, was given intragastrically in a clinically efficacious dose of 200 mg, the formation of the acids DOPAC and HVA was inhibited within perfusates of the caudate nucleus and nucleus accumbens. However, following disulfiram treatment, the proportion of alcohol metabolites did not differ from the control level in the untreated rat. The level of ALDH decreased by approximately 50% in these subcortical nuclei following the inhibition of the enzyme by disulfiram. Conversely, in samples of perfusate obtained from 14C-labeled sites within inferofrontal cortex, periform cortex, diagonal band of Broca, lateral-posterior caudate nucleus, tuberculum olfactorium, lateral olfactory tract or the olfactory nuclear complex, the proportion of DA metabolites remained stable. Generally, a low rate of deamination of the exogenously injected DA occurred within perfusion sites in the ventrobasal forebrain, whereas an intermediate rate of deamination was noted in samples collected at more dorsal loci. Thus, clearcut regional differences in DA catabolism occur in the brain of the living animal, which may depend upon the characteristics of the dopaminergic-rich area of the rat's brain.

Alcohols↗

PubMed1979

Disulfiram-induced acute organic brain syndrome.

Reversible acute organic brain syndrome is described in a patient receiving disulfiram, 250 mg daily. Slowing of the electroencephalogram (3 to 4 cycles per second) in the occipital region resolved ten days after discontinuation of disulfiram. Acute organic brain syndrome induced by disulfiram is not rare but is often not correlated, and it should always be considered a possibility in patients receiving disulfiram therapy.

Acute Disease↗

PubMed1979

The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.

Adolescent↗

PubMedDate not supplied

Inhibition of 1,2-dimethylhydrazine metabolism by disulfiram.

1. The effects of disulfiram on the metabolism of 1,2-dimethylhydrazine were studied in CDF rats. 2. Treatment with disulfiram causes enhanced elimination of azomethane in the expired air, inhibition of CO2 production, and decreased levels of 1,2-dimethylhydrazine metabolites in the urine. 3. These results suggest that disulfiram inhibits the N-oxidation of azomethane to azoxymethane, thus preventing further metabolism to the ultimate carcinogenic species, and provide an explanation for the observations that disulfiram inhibits 1,2-dimethylhydrazine-induced neoplasia of the large intestine.

Animals↗

PubMed1975

[Disulfiram and digestive motility; effect on absorption of ethanol in the rat].

The influence of disulfiram, ethanol and the association disulfiram-ethanol on gastro-intestinal motility and ethanol absorption was studied in rats. It was observed that disulfiram (25 mg/kg) and ethanol (0,8 g/kg), separately administered, decrease gastric emptying a nd increase propulsion in the small intestine; association of the two treatments results in the addition of the particular effects, except in the first intestinal segment. Disulfiram reduces ethanol absorption; very significant correlations have been noted between gastric emptying and ethanol absorption.

Animals↗

PubMed1977

The rapid reduction of disulfiram in blood and plasma.

A gas chromatographic assay procedure was developed to quantitate the reduction product of disulfiram, diethyldithiocarbamate (DDC), in blood and plasma. The procedure involved the in situ methylation of DDC prior to the extraction and chromatography of the methyl ester. The minimal sensitivity achieved was 0.2 microgram/ml from 1 ml of blood or plasma. The coefficient of variation about any concentration was 10.5%. Calibration curves having a reproducible nonlinear form were prepared up to 9 microgram/ml. The assay procedure was used to evaluate the stability of disulfiram and DDC in blood. Disulfiram was rapidly and quantitatively reduced to DDC within 4 minutes. The DDC thus formed decomposed in human and dog blood with half-lives of 70 and 100 minutes, respectively. The implications of these findings are discussed with respect to the chemical form of disulfiram responsible for the ethanol-sensitizing effect.

Animals↗

PubMed1977

A rapid and simple radioactive method for the determination of disulfiram and its metabolites from a single sample of biological fluid or tissue.

An analytical method is described for the determination of radioactive disulfiram, diethyldithiocarbamate, diethyldithiocarbamate-methyl ester, diethyldithiocarbamate-glucuronide, inorganic sulfate, and a protein bound S35 fraction from a single sample of either plasma, urine or tissue. The procedure is based upon quantitative stepwise extraction or precipitation of the individual compounds, and is both specific and precise. The applicability of the methods developed for the determination of S35 disulfiram and its S35 metabolites in plasma and urine from a dog given S35 disulfiram i.v., and in mouse brain from mice given S35 disulfiram i.p. are illustrated.

Animals↗

PubMed1977

Drug therapy reviews: management of the disulfiram-alcohol reaction.

A review of the proposed mechanisms of the disulfiram-alcohol interaction and recommended management of the interaction is presented. The efficacy of disulfiram in the management of alcoholism, the signs and symptoms of the disulfiram-alcohol interaction, and other agents with disulfiram-like activity are discussed. Recommended treatment consists of supportive measures such as Trendelenberg posture, administration of oxygen and intravenous infusion of fluid, solute, colloid, and, if needed, a pressor agent such as norepinephrine. Iron salts, ascorbic acid, antihistamines and phenothiazines are of no established benefit.

Acetaldehyde↗

PubMed1979

Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis.

Cerebrospinal fluid (CSF) dopamine-beta-hydroxylase (DBH) activity in 32 male alcoholics was measured using a modification of the radioenzymatic method of Molinoff et al. In most, the CSF was obtained before treatment with disulfiram, while in others it was obtained while they were on the drug (250 or 500 mg). As expected, treatment with this reversible DBH inhibitor had no effect on the activity of the enzyme measured in our in vitro assay. However, low pretreatment DBH activity was found to correlate with adverse reactions to disulfiram. Mean DBH activity of four individuals who went on to become psychotic on disulfiram was 0.13 +/- 0.02 nmole/ml per hr (mean +/- SEM). An additional four individuals who developed dysphoric but nonpsychotic reactions had a mean DBH of 0.23 +/- 0.03. Both these values were significantly lower than the mean DBH activity of the remaining 24 individuals treated with disulfiram who had no adverse side effects, 0.53 +/- 0.06 p less than 0.02 and p less than 0.05, respectively, 2-tailed t-test.

Adolescent↗