Pharmacology & toxicology
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Pharmacology & toxicology · Feb 2001
Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism.
Disulfiram is used in the treatment of chronic alcoholism, because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver aldehyde dehydrogenases. In addition, it is known that disulfiram also has some neurotoxic properties. ⋯ It is known that high doses of disulfiram may cause severe encephalopathy and peripheral neuropathy in humans, which could be attributed to the impairment of the metabolism of brain biogenic amines, due to inhibition of dopamine-beta-hydroxylase. Our experimental data show that disulfiram affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of aldehyde dehydrogenase. Therefore, in clinical practice 'disulfiram reaction' could still be achieved with a low dosage regimen not producing neurotoxicity