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Diss Factsheets
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EC number: 202-607-8 | CAS number: 97-77-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Exposure related observations in humans: other data
Administrative data
- Endpoint:
- exposure-related observations in humans: other data
- Type of information:
- other: review article
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented publication meeting basic scientific principles
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- Unnamed
- Year:
- 2 009
Materials and methods
- Type of study / information:
- Review on disulfiram: The anti-alcoholism drug disulfiram (Antabuse), which is an inhibitor of aldehyde dehydrogenase, induces an aversive reaction to alcohol consumption and thereby helps patients reduce alcohol intake.
- Endpoint addressed:
- basic toxicokinetics
- repeated dose toxicity: oral
- Principles of method if other than guideline:
- Recent clinical trials, initiated to investigate whether disulfiram could be used to treat individuals who abuse both alcohol and cocaine, have indicated that disulfiram effectively decreases cocaine consumption. Yet the ability of disulfiram to curb cocaine intake cannot be explained by the disruption of ethanol metabolism. Here, we synthesize clinical and animal data that point to dopamine β-hydroxylase inhibition as a mechanism underlying the efficacy of disulfiram in the treatment of cocaine dependence.
Test material
- Reference substance name:
- Disulfiram
- EC Number:
- 202-607-8
- EC Name:
- Disulfiram
- Cas Number:
- 97-77-8
- Molecular formula:
- C10H20N2S4
- IUPAC Name:
- disulfiram
- Details on test material:
- - Name of test material (as cited in study report): Disulfiram
Constituent 1
Method
- Details on study design:
- Review article
Results and discussion
- Results:
- Conclusion: Disulfiram has been used as an alcohol deterrent for decades, and recent studies indicate that it is also an effective pharmacotherapy for the treatment of cocaine dependence; however, the mechanisms behind its efficacy for alcohol and for cocaine addiction are distinct. Whereas aldehyde dehydrogenase is the primary target in treating alcoholism, human laboratory, genetic, and preclinical animal studies indicate that its beneficial effects on cocaine use result from the inhibition of dopamine b-hydroxylase (DBH). Despite the potential of DBH and its inhibition to modulate cocaine reward and aversion, the authors argue that the most important clinical effect of disulfiram-mediated DBH inhibition arises from the drug’s ability to reduce relapse, particularly, relapse precipitated by stress.
Any other information on results incl. tables
Disulfiram-Ethanol reaction:
Ethanol is converted to acetaldehyde by the enzyme alcohol dehydrogenase, and acetaldehyde is further metabolized to acetate by aldehyde dehydrogenase.Disulfiram is an inhibitor of aldehyde dehydrogenase. The high levels of acetaldehyde that accumulate following alcohol ingestion in patients taking disulfiram cause the mild to moderate levels of facial flushing, weakness, throbbing headache, nausea, vomiting, sweating, vertigo, hypotension, and other unpleasant symptoms that typify the disulfiram-ethanol reaction (also known as the Antabuse reaction).
Metabolism of disulfiram:
Upon absorption, disulfiram is immediately reduced to diethyldithiocarbamate (DDC) when it reacts with thiol groups. This metabolite of disulfiram is a potent copper chelator, and it can thereby affect the activity of copper-dependent enzymes such as monooxygenases, amine oxidase, cytochrome oxidase, microsomal carboxylesterase, and plasma cholinesterase.
Clinical trials:
To date, there have been eight supervised clinical trials, ranging from 56 to 270 days in duration, that assess oral disulfiram for the treatment of alcoholics. The percentage of disulfiram-treated patients who completed these trials, ranging from 18 to 58%, was higher for those populations in which drug administration was supervised by clinic staff or a family member. Only one study (comprising four disulfiram-treated patients and one placebo control) reported adverse side effects as a factor in patient drop-out. Four trials had a completely randomized design; three of these compared supervised versus unsupervised disulfiram administration (13–15). All groups reported better abstinence from drinking after supervised disulfiram administration compared with unsupervised administration or placebo.
Disulfiram Treatment for Dual Cocaine and Alcohol Dependence - Clinical Trials:
The groundbreaking trial addressed cocaine use both with and without comorbidity for alcohol abuse, showing that the benefits of disulfiram therapy were most pronounced in patients who either were not alcohol dependent at baseline or who fully abstained from alcohol during treatment. These observations directly suggest that disulfiram undermines cocaine addiction in a manner independent of its action in inhibiting alcohol intake.
Proposed Disulfiram inhibition of the norepinephrine (NE) biosynthetic pathway:
In the catecholamine synthesis pathway, tyrosine is converted into 3,4-dihydroxy-L-phenylalanine (L-DOPA) by tyrosine hydroxylase (TH), which is then transformed into dopamine by aromatic amino acid decarboxylase (AADC), whereupon dopamine b-hydroxylase (DBH) converts dopamine into norepinephrine. Disulfiram inhibits DBH, reducing the production of norepinephrine and increasing the pool of dopamine.
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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