antabuse 400mg tablets
We have previously reported a method for visualizing the mucosal surface of fixed unsectioned rodent colons at the crypt level and have identified lesions, termed aberrant crypt foci (ACF), in the colons of carcinogen-treated rodents. We hypothesized that ACF represent the precursor lesions (PL) of colon cancer. In the present study, the effect of feeding disulfiram (DSF) added to a semi-synthetic diet (0.5% or 1% by wt) on 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) induced ACF was investigated. DSF has been shown to inhibit DMH and AOM-induced colon cancer. Therefore, it was reasoned that if ACF represent PL then their induction and growth should also be inhibited by DSF. CF1 female mice were randomly divided into three groups of 30 each. Group 1 was fed a diet containing 1% DSF for 9 days prior to and 1 day after receiving a single i.p. injection of either DMH, AOM or saline. Group 2 was fed a diet containing 1% DSF for 9 days prior to and 14 days after receiving a single i.p. injection of DMH, AOM or saline, whereas group 3 received control diet throughout the experimental duration. All animals were killed 5 weeks after receiving the injections. It was observed that feeding DSF, for 9 days prior to and for either 1 day or 14 days after the administration of a single injection of DMH, resulted in a complete inhibition of ACF. DSF feeding for 9 days prior to and 1 day after AOM injection resulted in a significantly greater number of ACF compared to the control group (12 +/- 2.3 vs 7.2 +/- 1.2); whereas DSF feeding for a longer duration (i.e. 9 days prior to and 14 days after AOM treatment) was associated with a significantly lower number of ACF compared to those fed DSF for only one day after AOM treatment (4.1 +/- 0.6 vs 12.4 +/- 2.3) and a lower number compared to the control group (4.1 +/- 0.6 vs 7.2 +/- 1.2).
In clinical settings, veteran patients were likely to be dispensed either disulfiram or naltrexone for only several months or less. The contexts and reasons for these predominantly short-term treatment episodes or the benefits derived were not known and merit further study.
208 patients were randomized to disulfiram (250 mg/day), naltrexone (100 mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol.
antabuse online uk
A number of nutrients and chemicals have now been identified as consistent inducers of tibia dyschondroplasia (TD). Thiram, Antabuse, and fusarochromanone induce TD when fed at 30 to 75 ppm. Cysteine, cystine, homocysteine, and histidine induced TD when fed at .5 to 3% of the diet. Cation: anion imbalances resulting in acidotic diets also induced TD. Even though prevention of TD induced by these chemicals and nutrients has been established, reversal of the spontaneous TD lesion has not been clearly demonstrated. Thus, the etiology of the spontaneous lesion awaits elucidation. These model systems all suggest that TD is the result of decreased growth plate cartilage degradation. Recent work has shown that increased collagen cross-links in the accumulated cartilage, which makes collagen less susceptible to degradation. Cysteine-induced TD seems to decrease growth plate collagenase activity and production. A role of growth plate macrophages in paracrine signaling of collagenase production by chondrocytes has been presented.
antabuse half dose
To obtain and evaluate evidence about the supposed disulfiram-like interaction between metronidazole and ethanol.
Diphenylhydantoin (DPH) and tolbutamide serum levels were studied in ten volunteers before and after 4 days of disulfiram treatment. The mean DPH half life increased significantly from 11.0 +/- a.2 h to 19.0 +/- 3.3 h, and the mean DPH metabolic clearance rate decreased significantly from 51.2 +/- 17.2 ml/min to 33.9 +/- 12.0 ml/min during medication. No significant changes in the half life or metabolic clearance rate of tolbutamide was observed.
antabuse online cheap
20-Hydroxyleukotriene B4 was converted by rat liver homogenates in the presence of NAD+ to a more polar product on reverse-phase high-performance liquid chromatography. The product was identified as 20-carboxyleukotriene B4 by straight-phase high performance liquid chromatography, ultraviolet spectrophotometry and gas chromatography-mass spectrometry. The oxidative activity of the homogenates was located in the cytosol with an optimal pH of 8.0. The activity was dependent on NAD+, and NADP+ could not substitute for NAD+. 1 mol of 20-carboxyleukotriene B4 was formed with the reduction of 2 mol of NAD+. The reaction was inhibited by pyrazole and 4-methylpyrazole, inhibitors of alcohol dehydrogenase, and by various alcohols, such as ethanol, 12-hydroxylaurate, and 20-hydroxyprostaglandin E1. Disulfiram, an inhibitor of aldehyde dehydrogenase, also inhibited the activity. These results suggest that two discrete steps catalyzed by different enzymes, alcohol dehydrogenase and aldehyde dehydrogenase, are involved in the oxidation of 20-hydroxyleukotriene B4 in rat liver cytosol. The enzyme system seems to be different from that of human neutrophils.
The purpose of the present investigation was to evaluate methods to prevent the development of the immediate and delayed tissue damage in the injured spinal cord by early drug (disulfiram) interference with the molecular mechanism of tissue injury. The edematous inflammation as well as change in the levels and distribution of metallic ions like calcium following spinal cord contusion is known to contribute to the destructive process. A contusion model was applied in the spinal cord of rabbits using a pneumatic impactor. The effect of the systemically administered drug, disulfiram, in the traumatized spinal cord was determined by assaying the tissue water and Ca2+ contents at different locations of the spinal cord. A significant increase in the levels of the assayed parameters at the injured site of the spinal cord is markedly reduced by the pretreatment with disulfiram.
antabuse injection cost
We have studied the effect of disulfiram (DSF) solution containing 2-hydroxypropyl-beta-cyclodextrin and hydroxypropylmethylcellulose (DSF eye drops) on intraocular pressure (IOP) in experimentally induced ocular hypertension in rabbits. In both in vitro and in vivo transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while DSF was not detected. The amount of DDC penetration for 0.25% DSF eye drops was about 4-fold that for 0.1% DSF eye drops in in vivo transcorneal penetration experiments. The elevation in IOP was induced by the rapid infusion of 5% glucose solution (15 ml/kg of body weight) through the marginal ear vein, and IOP was measured with an electronic tonometer. The induced elevation in IOP was reduced by the instillation of 0.1-0.5% DSF eye drops, and the IOP-reducing effect increased with the increase in DSF concentration in the drops. Nitric oxide (NO) levels increased in the aqueous humor following the infusion of the 5% glucose solution, and this increase was also suppressed by the instillation of DSF eye drops. In conclusion, the present study demonstrates that the instillation of DSF eye drops has an IOP-reducing effect in rabbits with experimentally induced ocular hypertension, probably caused by the suppression of NO production.
antabuse drug classification
We report the case of a 51-year-old woman who developed disorganized speech, diminished communication, a decrease in appetite, and thoughts of suicide 10 days after she began taking disulfiram (250 mg/day), to which she added 1 glass of alcoholic beverage for 2 days. Delirium developed in association with an interaction between disulfiram and alcohol. The patient met DSM-IV criteria for major depressive disorder, alcohol dependence, and delirium.
antabuse online paypal
An experimentally validated computational model for hDBH, built in our lab, was used for structure-based, rational drug-design. The three-dimensional model was used for virtual-screening against small molecule databases from NCI, USA and elsewhere. Identified top hits were then tested in vitro against DBH with known inhibitors nepicastat and disulfiram as controls. Binding of the inhibitors to DBH were validated using fluorescence and CD spectroscopy as well as ITC. Pharmacokinetic analysis was performed computationally. Cyto- and hemo-toxicities of the lead compounds were assessed ex vivo. Finally. their anti-hypertensive efficacies were evaluated in L-NAME induced hypertensive rat model.
antabuse 125 mg
In combination with a low concentration (1 μM) of Cu2+, DS induced cytotoxicity in Raji cells with an IC50 of 0.085 ± 0.015 μM and in Molt4 cells with an IC50 of 0.435 ± 0.109 μM. The results of our animal experiments also showed that the mean tumor volume in DS/Cu-treated mice was significantly smaller than that in DS or control group, indicating that DS/Cu inhibits the proliferation of Raji cells in vivo. DS/Cu also induced apoptosis in 2 lymphoid malignant cell lines. After exposure to DS (3.3 μM)/Cu (1 μM) for 24 hours, apoptosis was detected in 81.03 ± 7.91% of Raji cells. DS/Cu induced significant apoptosis in a concentration-dependent manner with the highest apoptotic proportion (DS/Cu: 89.867 ± 4.69%) at a concentration of 2 μM in Molt4 cells. After 24 h exposure, DS/Cu inhibits Nrf2 expression. Flow cytometric analysis shows that DS/Cu induced ROS generation. DS/Cu induced phosphorylation of JNK and inhibits p65 expression as well as Nrf2 expression both in vitro and in vivo. N-acetyl-L-cysteine (NAC), an antioxidant, can partially attenuate DS/Cu complex-induced apoptosis and block JNK activation in vitro. In addition, NAC is able to restore Nrf2 nuclear translocation and p65 expression.
antabuse drug information
Factorial randomized double blind (for medication condition) clinical trial where CBT served as the platform and was delivered in weekly individual sessions in a community-based outpatient clinic. 99 outpatients who met DSM-IV criteria for current cocaine dependence were assigned to receive either disulfiram or placebo, and either CM or no CM. Cocaine and other substance use was assessed via a daily calendar with thrice weekly urine sample testing for 12 weeks with a one-year follow-up (80% interviewed at one year).
antabuse recommended dosage
Previous studies suggested that a relative dopamine (DA) deficiency may explain the altered LH secretory dynamics that occur in patients with polycystic ovary syndrome (PCO). These studies included findings of decreased urinary excretion of homovanillic acid (HVA), a metabolite of DA, and increased urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the major brain metabolite of norepinephrine. To further explore the role of DA in these patients, disulfiram (250 mg) was administered daily for 2 weeks to alter the conversion of DA to norepinephrine and to increase both peripheral and central DA in patients with PCO and in normal women. LH pulse frequency and amplitude and the serum LH response to GnRH were assessed before and during disulfiram administration. A dopaminergic effect during disulfiram administration was evidenced by a decrease in serum PRL in the PCO patients and an increase in urinary HVA excretion and a decrease in the ratio of 3-methoxy-4-hydroxyphenylglycol to HVA in urine in both groups (all P less than 0.05). This increase in DA did not significantly alter the serum estrogen level, the mean serum LH level, LH pulse amplitude, or serum LH responses to GnRH in either the PCO patients or the normal women. These data suggest that increasing endogenous DA does not correct the inappropriate gonadotropin secretion characteristic of PCO and places further doubt on the importance of DA in explaining the altered LH secretory dynamics in these patients.
antabuse with alcohol
The aliphatic alcohol 1,4-butanediol in converted into gamma-hydroxybutyric acid (GHB) via two enzymatic steps: first, it is oxidised by alcohol dehydrogenase in gamma-hydroxybutyraldehyde; second, the latter is transformed, likely by aldehyde dehydrogenase, into GHB. Initially, the present study compared the sedative/hypnotic effect of GHB and 1,4-butanediol, measured as loss of righting reflex. 1,4-Butanediol was more potent than GHB, presumably because of a more rapid penetration of the blood brain barrier. Further alcohol dehydrogenase inhibitors, 4-methylpyrazole and ethanol, totally prevented the sedative/hypnotic effect of 1,4-butanediol; the aldehyde dehydrogenase inhibitor disulfiram partially blocked the sedative/hypnotic effect of 1,4-butanediol. Finally, the sedative/hypnotic effect of 1,4-butanediol was antagonised by the GABA(B) receptor antagonists, SCH 50911 [(2S)(+)-5,5-dimethyl-2-morpholineacetic acid] and CGP 46381 [(3-aminopropyl)(cyclohexylmethyl)phosphinic acid], but not by the putative GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid), indicating that it is mediated by GABA(B) but not GHB receptors. Taken together, these results suggest that the sedative/hypnotic effect of 1,4-butanediol is mediated by its conversion in vivo into GHB which, in turn, binds to GABA(B) receptors. Accordingly 1,4-butanediol, unlike GHB, failed to displace [(3)H]GHB and [(3)H]baclofen in brain membranes.
antabuse 50 mg
The method used for CDTanalysis was IEF-PAGE. Sera of 49 males and 11 females aged 14-87 years, average age 46.85+/-18.53, were used in this study. Control group consisted of five patients who died after medical treatment that lasted longer than 15 days, and five patients who started Disulfiram therapy in controlled hospital environment.
antabuse 500 mg
Disulfiram (DSF), used since the 1950s in the treatment of alcoholism, is reductively activated to diethyldithiocarbamate and both compounds are thiol-reactive and readily complex copper. More recently DSF and copper-DSF (Cu-DSF) have been found to exhibit potent anticancer activity. We have previously shown that the anti-diabetic drug metformin is anti-proliferative and induces an intracellular reducing environment in oesophageal squamous cell carcinoma (OSCC) cell lines. Based on these observations, we investigated the effects of Cu-DSF and DSF, with and without metformin, in this present study. We found that Cu-DSF and DSF caused considerable cytotoxicity across a panel of OSCC cells, and metformin significantly enhanced the effects of DSF. Elevated copper transport contributes to DSF and metformin-DSF-induced cytotoxicity since the cell-impermeable copper chelator, bathocuproinedisulfonic acid, partially reversed the cytotoxic effects of these drugs, and interestingly, metformin-treated OSCC cells contained higher intracellular copper levels. Furthermore, DSF may target cancer cells preferentially due to their high dependence on protein degradation/turnover pathways, and we found that metformin further enhances the role of DSF as a proteasome inhibitor. We hypothesized that the lysosome could be an additional, novel, target of DSF. Indeed, this acid-labile compound decreased lysosomal acidification, and DSF-metformin co-treatment interfered with the progression of autophagy in these cells. In summary, this is the first such report identifying the lysosome as a target of DSF and based on the considerable cytotoxic effects of DSF either alone or in the presence of metformin, in vitro, and we propose these as novel potential chemotherapeutic approaches for OSCC.
antabuse user reviews
Hep3B, Huh7 and HepG2 hepatoma cells were incubated under normoxic (20% O2) or hypoxic (1% O2) conditions for 16 h. The expression and activity of HIF-1α and HIF-2α proteins were evaluated using immunoblotting and luciferase reporter assay, respectively. Semi-quantitative RT-PCR was used to analyze HIF-mediated gene expression. Endothelial tubule formation assay was used to evaluate the anti-angiogenic effect.
antabuse brand name
222 patients with chronic alcoholism (the second step of the disease) at the state of abstination and in the period of alcohol consumption were studied. In the course of treatment the patients received about 0.5 g of teturam per day within 4 months. In blood serum of the patients content of ethanol, malonic dialdehyde and activity of ethanol-oxidizing system (EOS) were estimated. In practically healthy persons, consuming no ethanol, no activity of EOS was noted as a rule. But in the patients with chronic alcoholism activity of EOS was 100-fold increased with simultaneous elevation in ethanol and malonic dialdehyde content in blood serum. After treatment with teturam content of ethanol, malonic dialdehyde and, especially, activity of the EOS were decreased in blood of the patients. After the treatment during 4 months activity of EOS was still distinctly higher in the patients than in healthy persons.
antabuse online pharmacy
The present study describes the NADPH-dependent, regioselective oxidation of diethyldithiocarbamate methyl ester (DDTC-Me), a dithiocarbamate ester containing both a thionosulfur (C = S) and a thioether (S-CH3) group, to two novel S-oxidized metabolites. DDTC-Me is a key metabolite in the overall bioactivation pathway for the clinically used alcohol deterrent, disulfiram. Incubation of DDTC-Me with rat liver microsomes resulted in the formation of two major metabolites. These metabolites were identified as DDTC-Me sulfoxide [S(O)CH3] and DDTC-Me sulfine (C = S+-O-) based on their NMR spectra and by MS. The formation of DDTC-Me sulfoxide was completely inhibited by the cytochrome P-450 inhibitors, emulgen 911 and 1-benzylimidazole, but only partially inhibited by heat inactivation of the flavin-containing moonooxygenases (FMO). This suggested that DDTC-Me sulfoxide formation is primarily catalyzed by cytochrome P-450 with a minor contribution from FMO. In contrast, the formation of DDTC-Me sulfine was inhibited from 60 to 80% in the presence of emulgen 911 and 1-benzylimidazole and 30 to 50% by heat inactivation of FMO, suggesting a partial role of FMO in the formation of DDTC-Me sulfine. DDTC-Me sulfoxide is a new class of dithiocarbamates that has not been previously described, whereas, DDTC-Me sulfine belongs to a class of thionosulfur sulfines that have been implicated in a number of toxicological processes.
antabuse 200 mg
The study population consisted of 60 doctors from the Free State Province, involved in the follow-up of alcoholics across various work settings.
antabuse implant cost
This paper presents a method for the analysis of drugs in dosage form. It is based on galvanostatic generation of oxidation agent from a suitable precursor on one segment of interdigitated microelectrode array (IDA) and its consecutive amperometric detection on second segment. High collection efficiency of this process in comparison to rotational ring disc electrode (RRDE) is a unique feature of IDA system. The transfer of oxidation agent can be influenced by addition of species, which reacts with oxidant. This influence can be used for its determination. Evaluation of generator-collector current dependence (diffusion layer titration curve) reveals the value of generator current I(genE) of the end-point of titration. I(genE) is proportional to the bulk phase concentration of determined species. The method was applied to the analysis of pharmaceuticals Antabus (Disulfiram Alpharma NOR, tetraethylthiuram disulfide (TETD)), a popular drug for alcoholism treatment, and Celaskon (vitamin C, Léciva CZE, ascorbic acid (AA)). From model samples analysis rather low detection limits, 9x10(-7) mol dm(-3), respectively, 4x10(-6) mol dm(-3), were estimated which enables trace content analysis of the drugs. A small size of IDA sensor also makes it suitable for microanalytical improvement.
antabuse cost uk
1. Subcellular fractionation of rat, guinea pig and human livers showed that aldehyde dehydrogenase metabolizing gamma-aminobutyraldehyde was exclusively localized in the cytoplasmic fraction in all three mammalian species. 2. Total gamma-aminobutyraldehyde activity of aldehyde dehydrogenase was found to be ca 0.41, 0.3 and 0.24 mumol NADH min-1 g-1 tissue, respectively in rat, guinea pig and human liver, with more than 95% of activity in the cytoplasm. 3. Partially purified cytoplasmic isozyme from rat liver showed similar chromatographic behavior and kinetic properties to the E3 isozyme isolated from human liver. 4. The rat isozyme was insensitive to disulfiram (40 microM) and to magnesium (160 microM) and had Km values of 5 microM (pH 7.4) for gamma-aminobutyraldehyde, 7.5 microM (pH 9.0) for propionaldehyde and 4 microM (pH 7.4) for NAD.
antabuse tablets 500mg
Retinoic acid and its isoforms are considered to be endogenous compounds which regulate embryonic development. In the work reported here we have determined which retinoids are present in zebrafish embryos and how their levels change throughout development and into adulthood. All-trans-RA is present and its level does not change significantly during embryogenesis. We failed to detect other retinoic acid isomers such as 9-cis-RA and 4-oxo-RA, but we did observe a rapid rise in the level of didehydroretinol after gastrulation. The most striking result is that the zebrafish embryo, like Xenopus and tunicates, contains a vast excess of t-retinal whereas the embryos of higher vertebrates have an excess of t-retinol. However, as the zebrafish grows, the levels of t-retinol rise so that by adulthood t-retinol and t-retinal concentrations are more equivalent, indicating a changing pattern of retinoid metabolism with growth. To examine the significance of the use of t-retinal as a precursor of t-RA we treated embryos with disulphiram, an inhibitor of retinaldehyde dehydrogenase. This resulted in embryos with an undulating notochord and correspondingly abnormal somites and ventral floor plate. In contrast to this effect, 4-methylpyrazole, which inhibits alcohol dehydrogenases, had no effect on development. This effect of disulphiram suggests that t-RA may be involved in the establishment of the anteroposterior axis of the embryo.
antabuse alcohol reaction
Women, compared with men, had poorer treatment outcomes on multiple measures of cocaine use during treatment and at post-treatment follow-up. These results appear to be primarily accounted for by disulfiram being less effective in women compared with men. There was no evidence of meaningful gender differences in outcome as a function of the behavioral therapies evaluated.
Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.
The effects of lithium and disulfiram on the 5-hydroxytryptamine (5-HT) system and hexobarbital (HX)-induced hypnosis were studied. Treatment with lithium significantly prolonged HX hypnosis. Disulfiram, a potent inhibitor of brain aldehyde dehydrogenase, also produced a prolongation of HX hypnosis. A combination of lithium treatment for 3 days with disulfiram synergistically potentiated the HX hypnosis and reduced the brain HX levels on awakening. Furthermore, L-tryptophan loading significantly increased the HX sleeping time and reduced the brain HX level on awakening in lithium-pretreated rats, whereas it had not effect on HX hypnosis in controls rats. L-Tryptophan also potentiated HX hypnosis in disulfiram-treated rats. The combination of L-tryptophan, lithium and disulfiram caused the greatest prolongation of HX hypnosis. However, no synergism between lithium and disulfiram was observed in animals treated with lithium for 5 days. after 3 days of lithium treatment, the rate of synthesis of 5-HT was elevated, whereas it had returned to the control level after 5 days of lithium treatment. Tryptophan loading increased the rate of synthesis of 5-HT more than 2-fold in control animals. The increase in the rate of 5-HT synthesis caused by lithium was further potentiated by tryptophan loading. These results suggest that lithium and disulfiram exert their synergistic effect on HX hypnosis by acting on the 5-HT system and that an accumulation of 5-hydroxyindoleacetaldehyde, an active metabolite of 5-HT, may be responsible for the increase in the brain sensitivity to barbiturates caused by these drugs.