Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new antabuse research articles will be listed here shortly after becoming available to us.
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Medical research on antabuse
Eksp Klin Farmakol. 2008 Mar-Apr; 71(2): 3-7
It has been shown that the peptide anxiolytic drug Selank recovers learning and memory impaired by damage of the noradrenergic (NA) brain system in Wistar rats after injection of the NA-synthesis inhibitor disulfiram, administration of neurotoxic compound 6-OHDA, or a combined induction of hypoxic hypoxia and hypercapnia. The main component of the Selank action is the stimulation of the search reflex aimed to distinguish an adequate adaptive response in the first trials of the learning session. The enhancement of memory consolidation and retrieval shows evidence for stimulation of the brain motivation mechanisms impaired by the NA system damage.
Expert Opin Ther Targets. 2008 Jun; 12(6): 739-48
Chen D, Dou QP
BACKGROUND: The conventional approach toward anticancer drug development is a time-consuming and expensive procedure. OBJECTIVE/METHODS: One approach to expedite this process and achieve more affordable means is to discover new applications of existing drugs, since their pharmacokinetics and pharmacological profiles are well known. RESULTS: Our encouraging findings in recent studies reveal anticancer activities of several copper-binding ligands including disulfiram (an antialcoholism drug), clioquinol (used to treat Alzheimer's and Huntington's diseases) and diethyldithiocarbamate (an agent for HIV-1 infection treatment). CONCLUSION: These in vitro and in vivo studies have demonstrated that these archaic drugs can target and react with tumor cellular copper, forming complexes that act as potent proteasome inhibitors and apoptosis inducers.
Disulfiram enhances subjective effects of dextroamphetamine in humans.
Pharmacol Biochem Behav. 2008 Sep; 90(3): 394-8
Sofuoglu M, Poling J, Waters A, Sewell A, Hill K, Kosten T
Disulfiram has shown promise in several clinical trials for cocaine addiction, but its potential utility in the treatment of amphetamine addiction has not been examined. The goal of this study was to determine the effects of disulfiram on acute physiological and subjective responses to dextroamphetamine in healthy volunteers. Five male and 5 female subjects participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects were randomly assigned to a sequence of disulfiram (250 mg/day) or placebo treatments each lasting for 4 days. Day four of each treatment period was the experimental session, in which subjects orally ingested a single dose of dextroamphetamine (20 mg/70 kg). Outcome measures included heart rate, blood pressure, plasma cortisol and prolactin, subjective and performance on the Sustained Attention to Response Test (SART). Disulfiram did not affect dextroamphetamine-induced increases in heart rate, blood pressure, cortisol, or prolactin. Disulfiram did enhance some of the subjective effects of dextroamphetamine including ratings of "high," "anxious," "bad drug effects," "want more drug" and "drug liking" and was also associated with decreased performance in the SART test. How these enhanced subjective amphetamine responses affect cocaine use behavior remains to be determined in future clinical trials.
JOP. 2008; 9(3): 350-3
Kast RE
Interleukin-18 (IL-18) is one of the mediators of both pancreas damage and systemic complications like hypotension and multi-organ dysfunction during acute pancreatitis. IL-18 is generated intracellularly from pro-IL-18 by caspase-1 mediated proteolysis. Active caspase-1 itself is generated intracellularly by the action of the inflammasome, autocatalysis and other stimuli. The anti-retroviral drug ritonavir inhibits conversion of inactive pro-caspase-1 to active caspase-1. Since ritonavir is well tolerated in short-term use it may therefore prove useful in treating acute pancreatitis by lowering caspase-1 mediated IL-18 formation and the many inflammatory mediators downstream from that. The alcoholism treatment drug disulfiram has been in continuous use since the 1950s. It likewise has a low risk profile. Disulfiram inhibits several human proteases, among them caspase-1. Given the current morbidity and mortality of pancreatitis, research should be directed to ritonavir and disulfiram as treatment options for illnesses like pancreatitis where excessive IL-18 contributes to pathology. The first clinically used angiotensin converting enzyme inhibitor, captopril, has shown potent caspase-1 inhibiting activity as well and should be investigated in rodent models of human pancreatitis.
Biol Pharm Bull. 2008 May; 31(5): 981-5
Nagai N, Ito Y, Takeuchi N
The ICR/f rat is a recessive-type hereditary cataractous strain, and opacity in the lens usually becomes evident at around 75 d of age. We previously found that the instillation of eye drops containing a disulfiram and hydroxypropyl-beta-cyclodextrin inclusion complex (DSF eye drops) delays lens opacification in ICR/f rats. In this study, we attempted to clarify the mechanisms of the delaying effect of DSF eye drops on cataract development in ICR/f rats. The calcium ion (Ca2+) content in the lenses of ICR/f rats increases at 77 d of age, and this elevation is preceded by a decrease in Ca2+-ATPase activity. On the other hand, the levels of nitric oxide (NO) and lipid peroxide (LPO) also increase in the lenses of ICR/f rats at 63 d of age, while the lenses are still transparent. The instillation of DSF eye drops reduces the changes in Ca2+ content, Ca2+-ATPase activity, NO and LPO levels in the lenses of ICR/f rats. The present study demonstrates that excessive NO production induces the increase in LPO, which causes the decrease in Ca2+-ATPase activity, and the increase in Ca2+ content in the lenses of ICR/f rat during cataract development. DSF eye drops have the ability to attenuate the increase in the NO and LPO levels, resulting in a delay in cataract development.
Tolerance to disulfiram induced by chronic alcohol intake in the rat.
Alcohol Clin Exp Res. 2008 Jun; 32(6): 937-41
Tampier L, Quintanilla ME, Israel Y
BACKGROUND: Disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism, is an effective medication when its intake is supervised by a third person. However, its therapeutic efficacy varies widely, in part due to the fact that disulfiram is a pro-drug that requires its transformation into an active form and because it shows a wide range of secondary effects which often prevent the use of doses that ensure full therapeutic effectiveness. In this preclinical study in rats we report the development of tolerance to disulfiram induced by the chronic ingestion of ethanol, an additional source of variation for the actions of disulfiram with possible therapeutic significance, We also addresses the likely mechanism of this effect. METHODS: Wistar-derived rats bred for generations as high ethanol drinkers (UChB) were trained for either 3 days (Group A) or 30 days (Group B) to choose between ethanol (10% v/v) or water, which were freely available from 2 bottles on a 24-hour basis. Subsequently, animals in both groups were administered disulfiram or cyanamide (another inhibitor of aldehyde dehydrogenase) and ethanol intake in this free choice paradigm was determined. Animals were also administered a standard dose of 1 g ethanol/kg (i.p) and arterial blood acetaldehyde was measured. RESULTS: Disulfiram (12.5 and 25 mg/kg) and cyanamide (10 mg/kg) markedly inhibited ethanol intake (up to 60 to 70%) in animals that had ethanol access for only 3 days (Group A). However both drugs were inactive in inhibiting ethanol intake in animals that had consumed ethanol for 30 days (Group B). Following the injection of 1 g ethanol/kg, arterial blood acetaldehyde levels reached levels of 150 and 300 microM for disulfiram and cyanamide respectively, values which were virtually identical regardless of the length of prior ethanol intake of the animals. CONCLUSIONS: Chronic ethanol intake in high-drinker rats leads to marked tolerance to the aversive effects of disulfiram and cyanamide on ethanol intake despite the presence of consistently high levels of blood acetaldehyde. These findings may have implications for the use of disulfiram for the treatment of alcoholism in humans.
[Pharmacological review of alcoholic dependence treatment.]
Vertex. 2008 Jan-Feb; 19(77): 512-21
Oural L, Paris MV, Sullivan O, Polach M, Pavlovsky F, Capece J
The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.
[Pharmacology of disulfiram - an update]
Fortschr Neurol Psychiatr. 2008 Apr; 76(4): 225-31
Mutschler J, Diehl A, Kiefer F
Recently, we have been observing an increase in prescription of Disulfiram requiring medical knowledge concerning the overall effects, side effects and drug interactions of this substance. In the following report, we give an overview about the pharmacology and the side effects of Disulfiram. As an example we demonstrate a case, in which an acute neurological deficit was misjudged as a side effect of Disulfiram. Furthermore, the potential of Disulfiram as a promising treatment in addiction medicine will be discussed.
Potantial utility of disulfiram against leishmaniasis.
Indian J Med Res. 2008 Feb; 127(2): 193-4
Namazi MR
Toxicology. 2008 May 21; 247(2-3): 139-44
Nagai N, Ito Y, Takeuchi N
Our previous studies have demonstrated that the instillation of eye drops containing disulfiram, a radical scavenger and nitric oxide synthase inhibitor, delays cataract development in ICR/f rats, and we have suggested that the production of nitric oxide (NO) and lipid peroxide (LPO) in the lens may relate to the delay in cataract development brought about by disulfiram. However, the involvement of NO and LPO in lenses of ICR/f rats during cataract development has not yet been established. In the present study, we determined changes in NO and LPO levels in lenses of ICR/f rats during cataract development. Opacification of ICR/f rat lenses started at 77 days of age, and the lenses of 91-day-old ICR/f rats were almost entirely opaque. The Ca(2+)-ATPase activity in the lenses of ICR/f rats decreased with increasing age, and an elevation in Ca(2+) content was observed in ICR/f rat lenses with the decrease in Ca(2+)-ATPase activity. NO levels in the lenses of ICR/f rats increased from 63 to 85 days of age, reaching a maximum at 77 days of age. In addition, LPO levels in the lenses of ICR/f rats also increased with increasing age. LPO levels in the lenses of 63- to 91-day-old ICR/f rats were found to be significantly higher compared with those in 22-day-old ICR/f rats. These changes of Ca(2+), Ca(2+)-ATPase, NO and LPO were attenuated by instillation of DSF eye drops. These results suggest that excessive NO may cause enhanced lipid peroxidation resulting in the inhibition of Ca(2+)-ATPase. The decrease in Ca(2+)-ATPase activity may cause the elevation in lens Ca(2+), leading to lens opacification in ICR/f rats.