Disulfiram Pathway


**Disulfiram is a drug used in the treatment of cocaine addiction and chronic alcoholism. With regards to cocaine addiction, cocaine inhibits dopamine reuptake by blocking dopamine transporter 1 (DAT1). This increases dopamine concentrations in the synapse and dopamine binding to its receptors induces euphoria. Disulfiram inhibits dopamine beta-hydroxylase, which metabolizes dopamine into norepinephrine. This causes more dopamine to accumulate in the axon terminal and more dopamine is released. When used concomitantly with cocaine, this causes an extremely high concentration of dopamine in the synapse that does not increase the euphoric effects of cocaine, but rather induces an unpleasant sensation of anxiety. This serves to discourage the patient from using cocaine while taking disulfiram.
With regards to alcoholism, disulfiram inhibits the mitochondrial enzyme acetaldehyde dehydrogenase, an enzyme involved in the second step of alcohol metabolism. This causes an increase in the levels of acetaldehyde, which leads to the development of symptoms of a hangover such as flushing, nausea, vomiting, headache, and confusion, which serves to discourage the patient from consuming alcohol while taking disulfiram.

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References

  1. Gaval-Cruz, M., and Weinshenker, D. (2009). Mechanisms of disulfiram-induced cocaine abstinence: Antabuse and cocaine relapse. Molecular Interventions, 9(4), 175-187. PMID: 19720750
  2. Kampman, K.M. (2009). New medications for the treatment of cocaine dependence. Ann Ist Super Sanita, 45(2), 109-115. PMID: 19636162