Conversely, disulfiram is a compound that exerts its effects via the same pharmacokinetic pathway associated with the ALDH2-2 allele (reviewed above). In the context of alcohol’s metabolism, disulfiram is an aldehyde dehydrogenase blocker that results in an increase in acetaldehyde after ingested alcohol is oxidized via ADH. This results in a dramatic change in subjective response to alcohol through a set of aversive symptoms caused by acetaldehyde buildup (e.g., nausea, flushing, and tachycardia). These acutely aversive consequences of alcohol consumption are thought to serve as a deterrent to alcohol consumption. Unfortunately, a major limitation of disulfiram’s use in practice is compliance (Suh et al., 2006); which is also problematic for other addiction pharmacotherapies (e.g., Kranzler et al., 2008). In summary, the biological and behavioral mechanisms of action of both naltrexone and disulfiram exemplify the potential utility of subjective response to alcohol as an endophenotype and its applications to treatment approaches for alcoholism.
