Inhibition of dopamine- β -hydroxylase by disulfiram

Goldstein, Menek; Anagnoste, B; Lauber, E.; McKereghan, M.R.

doi:10.1016/0024-3205(64)90031-1

Cited by 311 publications

(91 citation statements)

References 6 publications

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“…Most inhibitors of DBH, including disulfiram, chelate copper, thus depriving DBH of its required cofactor (Goldstein et al, 1964). Disulfiram inhibits DBH in animals, decreasing NE and increasing DA in both peripheral and central tissues (Musacchio et al, 1966;Karamanakos et al, 2001).…”

Section: Disulfiram and Cocaine Dependencementioning

confidence: 99%

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Weinshenker

Schroeder

2006

Neuropsychopharmacol

323

277

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Fueled by anatomical, electrophysiological, and pharmacological analyses of endogenous brain reward systems, norepinephrine (NE) was identified as a key mediator of both natural and drug-induced reward in the late 1960s and early 1970s. However, reward experiments from the mid-1970s that could distinguish between the noradrenergic and dopaminergic systems resulted in the prevailing view that dopamine (DA) was the primary 'reward transmitter' (a belief holding some sway still today), thereby pushing NE into the background. Most damaging to the NE hypothesis of reward were studies demonstrating that NE receptor antagonists and NE reuptake inhibitors failed to impact drug self-administration. In recent years new tools, such as genetically engineered mice, and new experimental paradigms, such as reinstatement of drug seeking following withdrawal, have propelled NE back into the awareness of addiction researchers. Of particular interest is disulfiram, an inhibitor of the NE biosynthetic enzyme dopamine b-hydroxylase, which has demonstrated promising efficacy in the treatment of cocaine dependence in preliminary clinical trials. The purpose of this review is to synthesize the new data linking NE to critical aspects of DA signaling and drug addiction, with a focus on psychostimulants (eg, cocaine), opiates (eg, morphine), and alcohol.

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Section: Disulfiram and Cocaine Dependencementioning

confidence: 99%

There and Back Again: A Tale of Norepinephrine and Drug Addiction

Weinshenker

Schroeder

2006

Neuropsychopharmacol

323

277

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“…Bathocuproine disulfonate has been reported to give a near complete inhibition at a concentration of 3 pM [12], and EDTA has been reported to give 50 inhibition at a concentration of 50-100 pM [ l l , 121. We tested these inhibitors in copper-free assay solutions, and found 50 % inhibition by both of them at concentrations of 0.2 -1 .O pM (assay systems b and d).…”

Section: Inhibition Of Enzyme Activity With Bathocuproine Disuljionatmentioning

confidence: 99%

The Enzyme‐Bound Copper of Dopamine β‐Monooxygenase

Skotland

Ljones

1979

European Journal of Biochemistry

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The enzyme‐bound copper of dopamine β‐monooxygenase reacted rapidly with the chelator bathocuproine disulfonate; the reaction in the presence of ascorbate was completed in 2 min at 25°C with 1 mM chelator. This reaction and also the reaction with EDTA could be used to prepare the apoenzyme, which in both cases was completely reactivated in less than 10 s. The reactivation data gave apparent Michaelis constants for copper of 0.03–0.2 μM. Trace amounts of copper in buffers and assay mixtures gave significant reactivation without added copper, unless they had been treated with a chelating resin. Titrations using the different chelation rates of free and enzyme‐bound copper indicated that four copper atoms are bound per enzyme molecule of four subunits. The native enzyme was more stable against thermal inactivation than the apoenzyme, but this stability was only partially restored by addition of copper to the apoenzyme.

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“…This hypothesis that CS2 acts on the metabolism of catecholamines gained support by reports that disulfiram (Goldstein, Anagnoste, Lauber & McKereghan, 1964;Musacchio, Kopin & Snyder, 1964) and diethyldithiocarbamate (DDC) (Carlsson, Lindquist, Fuxe & Hokfelt, 1966;Edington, 1968) inhibit dopamine-p-hydroxylase, and disulfiram is metabolized through DDC to CS2 (Johnston & Prickett, 1952;Fischer & Brantner, 1967). However, the effect of DDC is not restricted to dopamine-/3-hydroxylase.…”

Section: Introductionmentioning

confidence: 99%

The effects of carbon disulphide exposure on brain catecholamines in rats

Magós

1970

British J Pharmacology

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Summary1. Rats exposed to 2-0 mg/i. carbon disulphide (CS2) in the inspired air for 2 days, 4 h a day, showed a 13 % decrease in their brain noradrenaline concentration and a 16 % increase in their brain dopamine concentration. 2. After exposure for 5 or 10 days there was a further decrease in the concentration of noradrenaline in the brain, but brain dopamine returned to the control level. 3. In animals treated intraperitoneally with 2 0 mg/kg reserpine and exposed 2 and 3 days later to 20 mg/I. CS2 for 4 h per day, the brain dopamine concentration showed a 770/o increase compared with the unexposed reserpinized animals, but the noradrenaline concentration remained unchanged. 4. The dopamine concentrations in the adrenals after 10 days' exposure to 2-0 mg/I. CS2 were 67% to 100% higher than in the control animals. In reserpinized rats, 2 days' exposure to CS2 nearly trebled the dopamine content of adrenals. 5. Exposure to CS2 had no effect on the tyrosine concentration in the brain, and there was no change in the brain monoamine oxidase (MAO) activity.Tyrosine in the brain showed a 30 to 96% increase in concentration and MAO activity, using kynuramine as substrate, showed an approximately 5% increase 0-5 to 2 h after the subcutaneous administration of 500 mg/kg sodium diethyldithiocarbamate. 6. CS2 at 10-2M or lower concentrations had no inhibitory effect on the brain MAO activity in vitro. Diethyldithiocarbamate inhibited MAO at 10-2M, but not at 10-3M or lower concentrations. IntroductionCarbon disulphide (CS2) exposure can lead to widely different pathological conditions such as mental aberrations, hypertension, extrapyramidal symptoms and atherosclerosis (Quarelli, 1937; Gordy & Trumper, 1938;McDonald, 1938;Lewey, 1941a;Paluch, 1948;Vigliani & Pernis, 1955 ;Weist, 1957;Magos, 1961;Szobor, 1962). Recently, Tiller, Schilling & Morris (1968) have given statistical evidence on the increased frequency of death from coronary heart disease among viscose workers exposed to CS, and other toxic agents in this country.As catecholamines or drugs acting on catecholamine metabolism can influence brain functions and behaviour

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Inhibition of dopamine- β -hydroxylase by disulfiram

Cited by 311 publications

References 6 publications

There and Back Again: A Tale of Norepinephrine and Drug Addiction

There and Back Again: A Tale of Norepinephrine and Drug Addiction

The Enzyme‐Bound Copper of Dopamine β‐Monooxygenase

The effects of carbon disulphide exposure on brain catecholamines in rats

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