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Disulfiram

General Introduction Indications Mode of action Adverse reactions Warning and precaution References
Disulfiram
Disulfiram structure
CAS No.
97-77-8
Chemical Name:
Disulfiram
Synonyms
DSF;Ttd;Tts;Hoca;TATD;TETD;DRAM;NOXAL;TTS x;DRAM1
CBNumber:
CB0476519
Molecular Formula:
C10H20N2S4
Formula Weight:
296.54
MOL File:
97-77-8.mol

Disulfiram Properties

Melting point:
69-71 °C(lit.)
Boiling point:
117°C
Density 
1.27
refractive index 
1.5500 (estimate)
Flash point:
117°C/17mm
storage temp. 
Store at +4°C
solubility 
0.004g/l
form 
Crystals, Crystalline Powder or Granules
color 
Light yellow
Water Solubility 
0.02 g/100 mL
Merck 
14,3364
BRN 
1712560
Stability:
Stable. Incompatible with strong oxidants.
InChIKey
AUZONCFQVSMFAP-UHFFFAOYSA-N
CAS DataBase Reference
97-77-8(CAS DataBase Reference)
NIST Chemistry Reference
Disulfiram(97-77-8)
EPA Substance Registry System
Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), tetraethyl-(97-77-8)
SAFETY
  • Risk and Safety Statements
  • Hazard and Precautionary Statements (GHS)
Hazard Codes  Xn,N
Risk Statements  22-43-48/22-50/53
Safety Statements  24-37-60-61
RIDADR  UN 3077 9/PG 3
WGK Germany  3
RTECS  JO1225000
TSCA  Yes
HazardClass  9
PackingGroup  III
HS Code  29303000
Hazardous Substances Data 97-77-8(Hazardous Substances Data)
Toxicity LD50 orally in rats: 8.6 g/kg (Child, Cramp)
Symbol(GHS):
Signal word: Warning
Hazard statements:
Code Hazard statements Hazard class Category Signal word Pictogram P-Codes
H302 Harmful if swallowed Acute toxicity,oral Category 4 Warning P264, P270, P301+P312, P330, P501
H315 Causes skin irritation Skin corrosion/irritation Category 2 Warning P264, P280, P302+P352, P321,P332+P313, P362
H317 May cause an allergic skin reaction Sensitisation, Skin Category 1 Warning P261, P272, P280, P302+P352,P333+P313, P321, P363, P501
H319 Causes serious eye irritation Serious eye damage/eye irritation Category 2A Warning P264, P280, P305+P351+P338,P337+P313P
H361 Suspected of damaging fertility or the unborn child Reproductive toxicity Category 2 Warning P201, P202, P281, P308+P313, P405,P501
H370 Causes damage to organs Specific target organ toxicity, single exposure Category 1 Danger P260, P264, P270, P307+P311, P321,P405, P501
H372 Causes damage to organs through prolonged or repeated exposure Specific target organ toxicity, repeated exposure Category 1 Danger P260, P264, P270, P314, P501
H373 May cause damage to organs through prolonged or repeated exposure Specific target organ toxicity, repeated exposure Category 2 Warning P260, P314, P501
H400 Very toxic to aquatic life Hazardous to the aquatic environment, acute hazard Category 1 Warning P273, P391, P501
H410 Very toxic to aquatic life with long lasting effects Hazardous to the aquatic environment, long-term hazard Category 1 Warning P273, P391, P501
Precautionary statements:
P201 Obtain special instructions before use.
P202 Do not handle until all safety precautions have been read and understood.
P260 Do not breathe dust/fume/gas/mist/vapours/spray.
P264 Wash hands thoroughly after handling.
P264 Wash skin thouroughly after handling.
P270 Do not eat, drink or smoke when using this product.
P272 Contaminated work clothing should not be allowed out of the workplace.
P273 Avoid release to the environment.
P280 Wear protective gloves/protective clothing/eye protection/face protection.
P321 Specific treatment (see … on this label).
P391 Collect spillage. Hazardous to the aquatic environment
P307+P311 IF exposed: call a POISON CENTER or doctor/physician.
P333+P313 IF SKIN irritation or rash occurs: Get medical advice/attention.
P405 Store locked up.
P501 Dispose of contents/container to..…

Disulfiram price More Price(14)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 86720 Tetraethylthiuram disulfide ≥97.0% (S) 97-77-8 1kg $126 2018-11-13 Buy
Sigma-Aldrich 1224008 Disulfiram United States Pharmacopeia (USP) Reference Standard 97-77-8 200mg $348 2018-11-13 Buy
TCI Chemical B0479 Tetraethylthiuram Disulfide >97.0%(T) 97-77-8 25g $16 2018-11-22 Buy
TCI Chemical B0479 Tetraethylthiuram Disulfide >97.0%(T) 97-77-8 500g $57 2018-11-22 Buy
Alfa Aesar B20721 Tetraethylthiuram disulfide, 97% 97-77-8 250g $36.3 2018-11-13 Buy

Disulfiram Chemical Properties,Uses,Production

General Introduction

Alcohol dependence is a chronic disorder that may have multiple relapses and remissions, increased mortality and low long-term abstinence rates that lead to increased psychosocial losses. Many drugs have been used in the treatment of this disorder such as the anti-craving agents, acamprosate, naltrexone and the aversive agent, disulfiram[1, 2]. Disulfiram (trade name: Antabuse) has been in use since the early 1940s for the treatment of alcohol dependence and is the first FDA-approved medication for the treatment of this disorder[3,4,5]. Disulfiram has thus completed almost 60 years of use in alcohol use disorders and has stood the test of time[6]. A large number of studies have been done on this molecule, ever since some proving its superiority over other drugs while others negating it.
The mechanism of action of disulfiram is through inhibiting the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfiram blocks the oxidation of alcohol through irreversibly inactivating the aldehyde dehydrogenase, which acts in the second step of ethanol utilization[7].

Indications

Disulfiram is used as a second line treatment of alcohol dependence, behind acamprosate and naltrexone[8]. It is an aid for the management of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage. However, it should be noted that disulfiram is not a cure for alcoholism. When used alone, without proper motivation and supportive therapy, it is unlikely that it will have any substantive effect on the drinking pattern of the chronic alcoholic dependence[5]. Disulfiram should not be taken if alcohol has been consumed in the last 12 hours[9].
Recently, more and more studies have shown that disulfiram has the potential for the treatment of cancer[12, 13] and HIV infections[10, 11]. Disulfiram (DSF) can reactivate latent HIV-1 expression in a primary cell model of virus latency and has the potential to deplete the latent HIV-1 reservoir in patients on combination antiretroviral therapy. DSF can reactivate latent HIV-1 expression via the Akt signaling pathway through depletion of PTEN[10]. Recent studies have disclosed a surprising, but mechanistically consistent, anticancer activity of disulfiram. Disulfiram has been successfully used to suppress hepatic metastases originating from ocular melanoma[12]. The anticancer mechanism of disulfiram is through inhibiting the 26S proteasome (The orderly degradation of cellular proteins is critical for normal cell cycling and function, and inhibition of the proteasome pathway results in cell-cycle arrest and apoptosis)[12-14]. Moreover, disulfiram was also found to have specific activity against zinc fingers and RING-finger ubiquitin E3 ligases that play an important role in cancer development[12, 13].

Mode of action

Ethanol undergoes metabolism in the liver initially by alcohol dehydrogenase (ADH) forming acetaldehyde; this is removed from the body primarily by oxidation into acetate by acetaldehyde dehydrogenase (ALDH)[15], which finally enters the citric acid cycle. Disulfiram acts by inhibiting the enzyme ALDH via its metabolite S-methyl N, N-diethyl-dithio-carbamate-sulphoxide[16], leading to accumulation of acetaldehyde in blood. This gives rise to various manifestations of disulfiram-alcohol reaction (DER)[17]. Since the inhibition of ALDH by disulfiram is irreversible, the DER will get terminated only after production of new ALDH oncedisulfiram is stopped. The new ALDH takes about a week’s time to be produced. Hence patients should be advised to take alcohol only after 2 weeks of stopping disulfiram[18]. In addition to this, disulfiram also acts on the dopaminergic system, both disulfiram and its metabolite carbon disulfide leading to inhibition of dopamine beta-hydroxylase (DBH) that leads to increase in the levels of dopamine. This may give rise to several neuropsychiatric manifestations such as delirium, paranoia, impairment of memory, ataxia, dysarthria and frontal lobe release signs[19]. Besides this action, disulfiram is also known to inhibit dopamine beta-hydroxylase leading to an increase in dopamine concentrations but decreased norepinephrine in the brain[20]. This may suggest an anti-craving role of disulfiram in alcohol dependence[21].

Adverse reactions

In severe cases, hepatitis such as both cholestatic and fulminant hepatitis, as well as hepatic failure resulting in transplantation or death, could occur upon treatment of disulfiram[5]. In a small number of patients, side effects include a transient mild drowsiness, fatigability, impotence, headache, acneform eruptions, allergic dermatitis, or a metallic or garlic-like aftertaste during the first two weeks of therapy. These reactions often disappear spontaneously with the continuation of therapy, or with reduced dosage. High dosage, combined toxicity (with metronidazole or isoniazid), or to the unmasking of underlying psychoses can cause psychotic reactions[5].

Warning and precaution

The following tips should be pay attention during administration of disulfiram[9].
Disulfiram is not allowed if the patients have consumed alcohol within the past 12 hours. Do not drink alcohol while taking disulfiram and for up to 14 days after stop taking disulfiram.
It is not known whether disulfiram will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine. It is not known whether disulfiram passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine. People less than 18 years old should also disabled.
Disulfiram should not be used in the following cases:
Allergic people; those who have recently taken metronidazole (Flagyl) or paraldehyde; or have consumed any foods or products that contain alcohol;
People of the following cases should consult the doctors:
Liver or kidney disease; heart disease, high blood pressure, history of heart attack or stroke;
Underactive thyroid; diabetes; seizures or epilepsy; head injury or brain damage; a history of mental illness or psychosis; an allergy to rubber; or taking phenytoin (Dilantin), tuberculosis medicine, or a blood thinner (warfarin, Coumadin, Jantoven).

References

  1. Bouza, C., Angeles, M., Muñoz, A., & Amate, J. M. (2015). Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction, 99(7), 811-828.
  2. Laaksonen, E., Koskijännes, A., Salaspuro, M., Ahtinen, H., & Alho, H. (2008). A randomized, multicentre, open-label, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. Alcohol & Alcoholism, 43(1), 53.
  3. Petrakis, I.L., Nich, C. and Ralevski, E. (2006) Psychotic spectrum disorders and alcohol abuse: A review of pharmacotherapeutic strategies and a report on the effective-ness of naltrexone and disulfiram. Schizophrenia Bulletin, 32, 644-654.
  4. De Sousa, A. (2010) The pharmacotherapy of alcohol dependence: A state of the art review. Mens Sana Monographs, 8, 69-82.
  5. https://www.rxlist.com/antabuse-drug.htm
  6. Krampe, H., & Ehrenreich, H. (2010). Supervised disulfiram as adjunct to psychotherapy in alcoholism treatment. Current Pharmaceutical Design, 16(19), (60 years)
  7. Johansson, B. (1992) A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta Psychiatrica Scandanavica, 362, 15-26.
  8. https://www.ncbi.nlm.nih.gov/books/NBK459340/
  9. https://www.drugs.com/pro/disulfiram.html
  10. Doyon, G., Zerbato, J., Mellors, J. W., & Sluiscremer, N. (2013). Disulfiram reactivates latent hiv-1 expression through depletion of the phosphatase and tensin homolog. Aids, 27(2), F7-F11.
  11. Rasmussen, TA; Lewin, SR (July 2016). "Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents?". Current Opinion in HIV and AIDS.
  12. Cvek, B., & Dvorak, Z. (2008). The value of proteasome inhibition in cancer: can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor?. Drug Discovery Today, 13(15), 716-722.
  13. Kona, F. R., Buac, D., & A, M. B. (2011). Disulfiram, and disulfiram derivatives as novel potential anticancer drugs targeting the ubiquitin-proteasome system in both preclinical and clinical studies. Current Cancer Drug Targets, 11(3).
  14. Rajkumar, S. V., Richardson, P. G., Hideshima, T., & Anderson, K. C. (2005). Proteasome inhibition as a novel therapeutic target in human cancer. Journal of Clinical Oncology, 23(3), 630-639.
  15. Deitrich, R.A., Petersen, D. and Vasiliou, V. (2007) Removal of acetaldehyde from the body. Novartis Foundation Symposia, 285, 23-40.
  16. Pike, M.G., Mays, D.C., Macomber, D.W. and Lipsky, J.J. (2001) Metabolism of a disulfiram metabolite S-methyl N,N-diethyldithiocarbamate by flavinmonooxygenase in human renal microsomes. Drug Metabolism & Disposition, 29, 127-132.
  17. Larsen, V. (1948) The effects on experimental animals of antabuse (tetraethylthiuram disulfide) in combination with alcohol. Acta Pharmacologica Toxicology, 4, 321-332. 
  18. Krampe, H. and Ehrenreich, H. (2010) Supervised disulfiram as adjunct to psychotherapy in alcoholism treatment. Current Pharmaceutical Design, 16, 2076-2090. 
  19. Fuller, R.K. and Gordis, E. (2004) Does disulfiram have a role in alcoholism treatment today? Addiction, 99, 21-24. 
  20. Vaccari, A., Saba, P.L., Ruiu, S., Collu, M. and Devoto, P. (1996) Disulfiram and diethyldithiocarbamate intoxica-tion affects the storage and release of striatal dopamine. Toxicology & Applied Pharmacology, 139, 102-108. 
  21. Muller, C.A. and Banas, R. (2011) Disulfiram: An anti-craving substance? American Journal of Psychiatry, 168, 98. 

Chemical Properties

yellow-white crystals or grey powder

Uses

It is used as rubber accelerator; vulcanizer; seed disinfectant; fungicide; alcohol deterrent.

Uses

Alcohol deterrent;Dopamine beta-hydroxylase inhibitor

Uses

For the treatment and management of chronic alcoholism

Uses

Disulfiram is a copper and zinc chelator and an irreversible inhibitor of aldehyde dehydrogenase (IC50 = 0.1 mM) that has been indicated for the treatment of alcohol dependence. It also inhibits the copper-dependent enzyme dopamine β-hydroxylase, which prevents the breakdown of dopamine and has been considered as a treatment for cocaine dependence. When in complex with copper, disulfiram has been shown to inhibit purified 20S proteasome (IC50 = 7.5 μM) and 26S proteasome (IC50 = 20 μM) from MDA-MB-0231 breast cancer cells. Because disulfiram targets the ubiquitin-proteasome pathway, it has been investigated as an anti-cancer agent. Furthermore, at 250 nM it has been shown to induce reactive oxygen species, to activate JNK and p38 pathways, and to inhibit NF-κB activity, which suppresses self-renewal in cancer stem cells.

Definition

ChEBI: An organic disulfide that results from the formal oxidative dimerisation of N,N-diethyldithiocarbamic acid. A multi-enzyme inhibitor that is used in alcohol aversion therapy and also exhibits anticancer properties.

brand name

Antabuse (Odyssey) .

General Description

Odorless or almost odorless white or almost white to tan powder. Unpleasant taste with metallic or garlic aftertaste. pH of a solution obtained by shaking 1 g with 30 mL of water is 6 to 8.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

Disulfiram is sensitive to light. Disulfiram is incompatible with strong acids, strong oxidizers and nitrosating agents (e.g. N-Nitrosodiphenylamine). .

Hazard

Toxic symptoms when ingested with alcohol; animal teratogen. Vasodilation and nausea. Questionable carcinogen.

Fire Hazard

Flash point data for Disulfiram are not available; however, Disulfiram is probably combustible.

Biological Activity

Inhibitor of aldehyde dehydrogenase that displays antialcoholism activity. Shown to reversibly stimulated Ca 2+ -ATPase activity and inhibit V-ATPase (EC 50 = 26 μ M). Also inhibits expression of MMP-2 and MMP-9 and displays anti-invasive activity.

Contact allergens

TETD is a rubber accelerator of the thiuram group, contained in “thiuram mix.” It can cross-react with other thiurams, especially TMTD. TETD is used to aid those trying to break their dependence on alcohol. The disulfiram-alcohol reaction is not allergic but due to the accumulation of toxic levels of acetaldehyde. The implanted drug can, however, lead to local or generalized dermatitis, for example ingested disulfiram, mainly in previously rubber-sensitized patients. As an adjunctive treatment of alcoholism, it caused occupational contact dermatitis in a nurse.

Safety Profile

A human poison by ingestion. An experimental poison by intraperitoneal route. Toxic symptoms when accompanied by ingestion of alcohol. Human systemic effects by ingestion: jaundtce, joint changes. An experimental teratogen. Other experimental reproductive effects. Questionable carcinogen with experimental neoplastigenic data. See also THIRAM.

Disulfiram Preparation Products And Raw materials

Raw materials

Preparation Products


Disulfiram Suppliers

Global( 220)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Chemson Industrial (Shanghai) Co., Ltd.
86-21-65208861-ext8007
86-21-65180813 sales1@chemson.com.cn CHINA 121 58
Dalian Richfortune Chemicals Co., Ltd
86-411-84820922, 84821539
86-411-84821380 sales@richfortunechem.com China 362 57
Mainchem Co., Ltd.
+86-0592-6210733
+86-0592-6210733 sales@mainchem.com CHINA 32651 55
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 956 58
Chemwill Asia Co.,Ltd.
86-21-51086038
86-21-51861608 chemwill_asia@126.com;sales@chemwill.com;chemwill@hotmail.com;chemwill@gmail.com CHINA 24118 58
Hubei Jusheng Technology Co.,Ltd.
86-188-71490254
peter@hubeijusheng.com CHINA 20229 58
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 19997 58
J & K SCIENTIFIC LTD. 400-666-7788 +86-10-82848833
+86-10-82849933 jkinfo@jkchemical.com;market6@jkchemical.com China 96815 76
Meryer (Shanghai) Chemical Technology Co., Ltd. +86-(0)21-61259100(Shanghai) +86-(0)755-86170099(ShenZhen) +86-(0)10-62670440(Beijing)
+86-(0)21-61259102(Shanghai) +86-(0)755-86170066(ShenZhen) +86-(0)10-88580358(Beijing) sh@meryer.com China 40395 62
Beijing Donghualituo Techonlogy Development Co.,Ltd. 010-88425576
(+86)-10-88425546 sales@dhltchem.com China 795 59

View Lastest Price from Disulfiram manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2018-07-25 Disulfiram
97-77-8
US $100.00 / KG 100G 98% 10KG,20KG career henan chemical co
2018-04-23 Accelerator TETD; Disulfiram; Tetraethylthiuramdisulfide
97-77-8
US $4.00 / KG 25KG 99.50% 1000tons Chemson Industrial (Shanghai) Co., Ltd.

Disulfiram Spectrum


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