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EC number: 202-607-8
CAS number: 97-77-8
Ethanol is converted to acetaldehyde by the enzyme alcohol
dehydrogenase, and acetaldehyde is further metabolized to acetate by
aldehyde dehydrogenase.Disulfiram is an inhibitor of aldehyde
dehydrogenase. The high levels of acetaldehyde that accumulate following
alcohol ingestion in patients taking disulfiram cause the mild to
moderate levels of facial flushing, weakness, throbbing headache,
nausea, vomiting, sweating, vertigo, hypotension, and other unpleasant
symptoms that typify the disulfiram-ethanol reaction (also known as the
Metabolism of disulfiram:
Upon absorption, disulfiram is immediately reduced to
diethyldithiocarbamate (DDC) when it reacts with thiol groups. This
metabolite of disulfiram is a potent copper chelator, and it can thereby
affect the activity of copper-dependent enzymes such as monooxygenases,
amine oxidase, cytochrome oxidase, microsomal carboxylesterase, and
To date, there have been eight supervised clinical trials, ranging
from 56 to 270 days in duration, that assess oral disulfiram for the
treatment of alcoholics. The percentage of disulfiram-treated patients
who completed these trials, ranging from 18 to 58%, was higher for those
populations in which drug administration was supervised by clinic staff
or a family member. Only one study (comprising four disulfiram-treated
patients and one placebo control) reported adverse side effects as a
factor in patient drop-out. Four trials had a completely randomized
design; three of these compared supervised versus unsupervised
disulfiram administration (13–15). All groups reported better abstinence
from drinking after supervised disulfiram administration compared with
unsupervised administration or placebo.
Disulfiram Treatment for Dual Cocaine and Alcohol Dependence -
The groundbreaking trial addressed cocaine use both with and
without comorbidity for alcohol abuse, showing that the benefits of
disulfiram therapy were most pronounced in patients who either were not
alcohol dependent at baseline or who fully abstained from alcohol during
treatment. These observations directly suggest that disulfiram
undermines cocaine addiction in a manner independent of its action in
inhibiting alcohol intake.
Proposed Disulfiram inhibition of the norepinephrine (NE)
In the catecholamine synthesis pathway, tyrosine is converted into
3,4-dihydroxy-L-phenylalanine (L-DOPA) by tyrosine hydroxylase (TH),
which is then transformed into dopamine by aromatic amino acid
decarboxylase (AADC), whereupon dopamine b-hydroxylase (DBH) converts
dopamine into norepinephrine. Disulfiram inhibits DBH, reducing the
production of norepinephrine and increasing the pool of dopamine.
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