A preliminary report on antabuse therapy for alcoholism

Steckler, Philip P.; Harris, Lebert

doi:10.1007/bf01584266

Cited by 3 publications

(3 citation statements)

References 3 publications

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“…The evidence for a role of AcH in the etiology of alcoholinduced cardiomyopathy is based almost entirely on experimental animal data (Liang et al, 1999;Ren et al, 2000;Schreiber et al, 1974;Segel and Mason 1979;Tomaru et al, 1983).Human indications of cardiac injury come from observations of the combination of alcohol drinking and the use of cyanamide (Beermann and Edelstam, 1986) or disulfiram (Steckler and Harris, 1951; see reviews by Chick 1999;Wright and Moore 1990) and from one study in which circulating antibodies to cardiac protein-AcH adducts were associated with alcoholic heart muscle disease (Harcombe et al, 1995). Elevated AcH levels (Eriksson et al, 1996) and the smaller threshold dose for the development of alcoholic cardiomyopathy in women compared with men (Kupari and Koskinen, 1992;Urbano-Márquez et al, 1995) also support the role of AcH in the pathological actions of alcohol in the heart.…”

Section: Chronic Pathological Effects Of Alcohol Drinkingmentioning

confidence: 98%

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

Eriksson

2001

Alcoholism Clin & Exp Res

227

116

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Background: Recent advances in the field of acetaldehyde (AcH) research have raised the need for a comprehensive review on the role of AcH in the actions of alcohol. This update is an attempt to summarize the available AcH research.Methods: The descriptive part of this article covers not only recent research but also the development of the field. Special emphasis is placed on mechanistic analyses, new hypotheses, and conclusions.Results: Elevated AcH during alcohol intoxication causes alcohol sensitivity, which involves vasodilation associated with increased skin temperature, subjective feelings of hotness and facial flushing, increased heart and respiration rate, lowered blood pressure, sensation of dry mouth or throat associated with bronchoconstriction and allergy reactions, nausea and headache, and also reinforcing reactions like euphoria. These effects seem to involve catecholamine, opiate peptide, prostaglandin, histamine, and/or kinin mechanisms. The contribution of AcH to the pathological consequences of chronic alcohol intake is well established for different forms of cancer in the digestive tract and the upper airways. AcH seems to play a role in the etiology of liver cirrhosis. AcH may have a role in other pathological developments, which include brain damage, cardiomyopathy, pancreatitis, and fetal alcohol syndrome. AcH creates both unpleasant aversive reactions that protect against excessive alcohol drinking and euphoric sensations that may reinforce alcohol drinking. The protective effect of AcH may be used in future treatments that involve gene therapy with or without liver transplantation.Conclusions: AcH plays a role in most of the actions of alcohol. The individual variability in these AcH-mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcHmetabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.

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Section: Chronic Pathological Effects Of Alcohol Drinkingmentioning

confidence: 98%

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

Eriksson

2001

Alcoholism Clin & Exp Res

227

116

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“…A similar behavior has been found in the case of thiuramdisulfides, which exhibit considerable reactivity toward thiols and possess a particular follow-on chemistry. The compound disulfiram (1,1′,1″,1‴-[disulfanediylbis(carbonothioylnitrilo)]tetraethane, tetraethylthiuramdisulfide), for instance, is a highly reactive, thiol-specific reagent, which in the past has been used under the name Antabuse to treat alcoholism (Figure ). , Disulfiram metabolites react with key cysteine residues in the human target enzyme aldehyde dehydrogenase, which is subsequently inhibited (Figure B). In the presence of ethanol, this particular inhibition results in an accumulation of acetaldehyde in the body and a range of unpleasant physiological effects.…”

Section: From Simple Disulfides To Highly Reactive Sulfur Speciesmentioning

confidence: 99%

Control of Oxidative Posttranslational Cysteine Modifications: From Intricate Chemistry to Widespread Biological and Medical Applications

Jacob

Battaglia²,

Burkholz

et al. 2011

Chem. Res. Toxicol.

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Cysteine residues in proteins and enzymes often fulfill rather important roles, particularly in the context of cellular signaling, protein-protein interactions, substrate and metal binding, and catalysis. At the same time, some of the most active cysteine residues are also quite sensitive toward (oxidative) modification. S-Thiolation, S-nitrosation, and disulfide bond and sulfenic acid formation are processes which occur frequently inside the cell and regulate the function and activity of many proteins and enzymes. During oxidative stress, such modifications trigger, among others, antioxidant responses and cell death. The unique combination of nonredox function on the one hand and participation in redox signaling and control on the other has placed many cysteine proteins at the center of drug design and pesticide development. Research during the past decade has identified a range of chemically rather interesting, biologically very active substances that are able to modify cysteine residues in such proteins with huge efficiency, yet also considerable selectivity. These agents are often based on natural products and range from simple disulfides to complex polysulfanes, tetrahydrothienopyridines, α,β -unsaturated disulfides, thiuramdisulfides, and 1,2-dithiole-3-thiones. At the same time, inhibition of enzymes responsible for posttranslational cysteine modifications (and their removal) has become an important area of innovative drug research. Such investigations into the control of the cellular thiolstat by thiol-selective agents cross many disciplines and are often far from trivial.

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“…The evidence for a role of AcH in the etiology of alcoholinduced cardiomyopathy is based almost entirely on experimental animal data (Liang et al, 1999;Ren et al, 2000;Schreiber et al, 1974;Segel and Mason 1979;Tomaru et al, 1983).Human indications of cardiac injury come from observations of the combination of alcohol drinking and the use of cyanamide (Beermann and Edelstam, 1986) or disulfiram (Steckler and Harris, 1951;see reviews by Chick 1999;Wright and Moore 1990) and from one study in which circulating antibodies to cardiac protein-AcH adducts were associated with alcoholic heart muscle disease (Harcombe et al, 1995). Elevated AcH levels (Eriksson et al, 1996) and the smaller threshold dose for the development of alcoholic cardiomyopathy in women compared with men (Kupari and Koskinen, 1992;Urbano-Márquez et al, 1995) also support the role of AcH in the pathological actions of alcohol in the heart.…”

Section: Chronic Pathological Effects Of Alcohol Drinkingmentioning

confidence: 99%

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

2001

Alcoholism: Clinical and Experimental Research

138

102

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AcH plays a role in most of the actions of alcohol. The individual variability in these AcH-mediated actions will depend on the genetic polymorphism, not only for the alcohol and AcH-metabolizing enzymes but also for the target sites for AcH actions. The subtle balance between aversive and reinforcing, protecting and promoting factors will determine the overall behavioral and pathological developments.

show abstract

A preliminary report on antabuse therapy for alcoholism

Cited by 3 publications

References 3 publications

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

Control of Oxidative Posttranslational Cysteine Modifications: From Intricate Chemistry to Widespread Biological and Medical Applications

The Role of Acetaldehyde in the Actions of Alcohol (Update 2000)

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