-
BMJ (Clinical Research Ed.) Aug 1989
-
Tijdschrift Voor Psychiatrie 2012Cocaine abuse and dependency have a considerable impact on society and health issues. Current treatment of cocaine dependency consists primarily of psychosocial and... (Review)
Review
BACKGROUND
Cocaine abuse and dependency have a considerable impact on society and health issues. Current treatment of cocaine dependency consists primarily of psychosocial and therapeutic interventions. There is a marked need for effective pharmacological treatments in addition to the currently available treatment options. Recently, there is some evidence that disulfiram (DSF) might reduce use of cocaine in patients presenting with cocaine dependency.
AIM
To explore the efficacy of disulfiram as a treatment for cocaine dependency.
METHOD
We performed a Medline search for randomised controlled trials (RCTs) relating to disulfiram as a treatment for cocaine dependency.
RESULTS
We found six RCT’s for this review. Disulfiram seemed to have a positive effect on the primary cocaine outcomes. In addition, a positive effect of disulfiram seemed to be independent of alcohol abuse. However, the quality of these studies was extremely variable both in terms of sample size and composition. A possible neurobiological explanation for this would be an inhibitory effect of disulfiram on dopamine beta-hydroxylase, thus generating lower levels of norepinefrine.
CONCLUSION
Disulfiram seems to be a valuable drug for the treatment of cocaine dependency. Due to the limited number and quality of the published studies, further research is needed in order to support the early positive results.
Topics: Cocaine-Related Disorders; Disulfiram; Dopamine beta-Hydroxylase; Enzyme Inhibitors; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22237610
DOI: No ID Found -
Systematic Reviews Jun 2022Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and...
BACKGROUND AND OBJECTIVES
Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Disulfiram (DSF), as an anti-alcoholic drug, kills the cancer cells by inducing apoptosis. Several preclinical and clinical studies have examined the potential of repurposing DSF as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans.
METHODS
Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics.
RESULTS
Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates, separately. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule. There was no noticeable body weight loss after DSF treatment, which indicated that there was no major toxicity of DSF.
CONCLUSIONS
This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.
Topics: Animals; Antineoplastic Agents; Disulfiram; Humans; Neoplasms
PubMed: 35655266
DOI: 10.1186/s13643-021-01858-4 -
Biochemical Pharmacology Dec 2020Hydrogen sulfide (HS) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase...
BACKGROUND
Hydrogen sulfide (HS) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST) are the principal enzymes responsible for its biogenesis. A recent yeast screen suggested that disulfiram (a well-known inhibitor of aldehyde dehydrogenase and a clinically used drug in the treatment of alcoholism) may inhibit CBS in a cell-based environment. However, prior studies have not observed any direct inhibition of CBS by disulfiram. We investigated the potential role of bioconversion of disulfiram to bis(N,N-diethyldithiocarbamate)-copper(II) complex (CuDDC) in the inhibitory effect of disulfiram on HS production and assessed its effect in two human cell types with high CBS expression: HCT116 colon cancer cells and Down syndrome (DS) fibroblasts.
METHODS
HS production from recombinant human CBS, CSE and 3-MST was measured using the fluorescent HS probe AzMC. Mouse liver homogenate (a rich source of CBS) was also employed to measure HS biosynthesis. The interaction of copper with accessible protein cysteine residues was evaluated using the DTNB method. Cell proliferation and viability were measured using the BrdU and MTT methods. Cellular bioenergetics was evaluated by Extracellular Flux Analysis.
RESULTS
While disulfiram did not exert any significant direct inhibitory effect on any of the HS-producing enzymes, its metabolite, CuDDC was a potent inhibitor of CBS and CSE. The mode of its action is likely related to the complexed copper molecule. In cell-based systems, the effects of disulfiram were variable. In colon cancer cells, no significant effect of disulfiram was observed on HS production or proliferation or viability. In contrast, in DS fibroblasts, disulfiram inhibited HS production and improved proliferation and viability. Copper, on its own, failed to have any effects on either cell type, likely due to its low cell penetration. CuDDC inhibited HS production in both cell types studied and exerted the functional effects that would be expected from a CBS inhibitor: inhibition of cell proliferation of cancer cells and a bell-shaped effect (stimulation of proliferation at low concentration and inhibition of these responses at higher concentration) in DS cells. Control experiments using a chemical HS donor showed that, in addition to inhibiting CBS and CSE, part of the biological effects of CuDDC relates to a direct reaction with HS, which occurs through its complexed copper.
CONCLUSIONS
Disulfiram, via its metabolite CuDDC acts as an inhibitor of CBS and a scavenger of HS, which, in turn, potently suppresses HS levels in various cell types. Inhibition of HS biosynthesis may explain some of the previously reported actions of disulfiram and CuDDC in vitro and in vivo. Disulfiram or CuDDC may be considered as potential agents for the experimental therapy of various pathophysiological conditions associated with HS overproduction.
Topics: Acetaldehyde Dehydrogenase Inhibitors; Animals; Cell Survival; Chelating Agents; Copper; Cystathionine beta-Synthase; Disulfiram; Ditiocarb; Dose-Response Relationship, Drug; Female; HCT116 Cells; Humans; Liver; Mice; Mice, Inbred BALB C; Organometallic Compounds
PubMed: 33035509
DOI: 10.1016/j.bcp.2020.114267 -
Indian Journal of Pharmacology 2022
Topics: Alcohol Drinking; Alcoholism; Disulfiram; Eating; Humans; Ischemia; Myocardial Ischemia
PubMed: 35546467
DOI: 10.4103/ijp.ijp_930_21 -
Alcohol Research & Health : the Journal... 2008Developing pharmacotherapies to treat alcohol dependence and associated health problems traditionally has been based on gaining a better understanding of the... (Review)
Review
Developing pharmacotherapies to treat alcohol dependence and associated health problems traditionally has been based on gaining a better understanding of the neuroscience underlying alcohol-drinking behavior. To date, three medications have been approved for the treatment of alcohol dependence: disulfiram (Antabuse®), naltrexone (Revia®, Vivitrol®, and Naltrel®), and acamprosate (Campral®). However, these medications have modest efficacy, and there is a great need for newer medications that target different neurochemical systems and which could be used either as adjunctive treatments or to treat subpopulations of drinkers. Furthermore, it also is important to improve current treatment options by understanding and incorporating differences in how people with certain genes respond to medication (i.e., pharmacogenetic differences).
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Brain Chemistry; Disulfiram; Humans; Naltrexone; Narcotic Antagonists; Taurine; Treatment Outcome
PubMed: 23584013
DOI: No ID Found -
Communications Biology Aug 2023The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments....
The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. Antibiotic adjuvant strategy is a more effective and economical approach to expand the lifespan of currently used antibiotics. Herein, we uncover that alcohol-abuse drug disulfiram (DSF) and derivatives thereof are potent antibiotic adjuvants, which dramatically potentiate the antibacterial activity of carbapenems and colistin against New Delhi metallo-β-lactamase (NDM)- and mobilized colistin resistance (MCR)-expressing Gram-negative pathogens, respectively. Mechanistic studies indicate that DSF improves meropenem efficacy by specifically inhibiting NDM activity. Moreover, the robust potentiation of DSF to colistin is due to its ability to exacerbate the membrane-damaging effects of colistin and disrupt bacterial metabolism. Notably, the passage and conjugation assays reveal that DSF minimizes the evolution and spread of meropenem and colistin resistance in clinical pathogens. Finally, their synergistic efficacy in animal models was evaluated and DSF-colistin/meropenem combination could effectively treat MDR bacterial infections in vivo. Taken together, our works demonstrate that DSF and its derivatives are versatile and potent colistin and carbapenems adjuvants, opening a new horizon for the treatment of difficult-to-treat infections.
Topics: Animals; Colistin; Carbapenems; Meropenem; Disulfiram; Anti-Bacterial Agents; Drug Combinations; Gram-Negative Bacteria
PubMed: 37537267
DOI: 10.1038/s42003-023-05173-7 -
International Journal of Molecular... Jan 2023In the process of assisted reproduction, the high-oxygen in vitro environment can easily cause oxidative damage to oocytes. Disulfiram (DSF) can play an anti-oxidant or...
In the process of assisted reproduction, the high-oxygen in vitro environment can easily cause oxidative damage to oocytes. Disulfiram (DSF) can play an anti-oxidant or pro-oxidant role in different cells, and the effect of DSF on oocytes remains unclear. Moreover, it remains unclear whether the use of DSF in the early stages of pregnancy has a negative impact on the fetus. In this study, we found that DSF increased serum FSH levels and increased the ovulation rate in mice. Moreover, DSF enhanced the antioxidant capacity of oocytes and contributed to the success rate of in vitro fertilization. Moreover, the use of DSF in early pregnancy in mice increased the uterine horn volume and the degree of vascularization, which contributed to a successful pregnancy. In addition, it was found that DSF regulated the mRNA expression of angiogenesis-related genes (), follicular development-related genes (, and ), ovulation-related genes (, and ) and antioxidant-related genes ( and ). These results indicate that DSF is helpful for increasing the antioxidant capacity of oocytes and the ovulation rate. In early pregnancy in mice, DSF promotes pregnancy by increasing the degree and volume of uterine vascularization.
Topics: Mice; Female; Animals; Disulfiram; Antioxidants; Oxidative Stress; Reactive Oxygen Species; Reproduction; Cell Line, Tumor
PubMed: 36768698
DOI: 10.3390/ijms24032371 -
Addiction Science & Clinical Practice Feb 2015Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological... (Review)
Review
Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological treatment is effective for decreasing alcohol consumption and promoting abstinence. However, unique factors belonging to HCV-infected individuals, such as baseline hepatic vulnerability and possible ongoing hepatitis C treatment, complicate AUD drug therapy. The goal of this review is to systematically identify, summarize, and evaluate the existing evidence on the pharmacological management of AUD in HCV-infected individuals. MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for English- and French-language articles published from 1993 to December 2013. The search criteria focused on clinical trials and observational studies assessing the efficacy and/or safety of pharmacological management of AUD in patients infected with HCV. Of 421 identified studies, three were included for analysis. Two were observational studies assessing the safety of disulfiram. One was a randomized controlled trial assessing the efficacy and safety of baclofen. There is paucity of data regarding the efficacy and safety of pharmacological treatment of AUD in HCV-infected individuals, with studies being small series and showing significant heterogeneity. No strong recommendations can be made based on the current studies as to which pharmacological option should be preferred in this sub-population.
Topics: Alcohol Deterrents; Alcohol-Related Disorders; Baclofen; Disulfiram; Hepatitis C; Humans; Transaminases
PubMed: 25928362
DOI: 10.1186/s13722-015-0029-2 -
British Medical Journal Jun 1953
Topics: Behavior, Addictive; Disulfiram; Humans; Substance-Related Disorders
PubMed: 13042308
DOI: 10.1136/bmj.1.4825.1450-c