Associate editor: D.M. LovingerPharmacological treatment of alcohol dependence: Target symptoms and target mechanisms
Section snippets
Alcohol dependence—a chronic relapsing disease
Substance use disorders continue to be viewed by many as defects of character not amenable to medical treatments. One of the objectives of the present paper is to reinforce the point so well argued by others (McLellan et al., 2000) that drug and alcohol dependence are, in fact, chronic relapsing disorders which share numerous characteristics with other chronic relapsing medical conditions such as hypertension, diabetes or asthma. While it is true that alcoholism cannot be treated without regard
Disulfiram
For many years, disulfiram was the only medication available to aid sobriety. Disulfiram blocks the enzyme aldehyde dehydrogenase, leading to an accumulation of acetaldehyde following intake of alcohol. This in turn causes flushing, shortness of breath, tachycardia, headache and nausea. It has been thought that anticipation of these symptoms would help patients abstain from alcohol. Importantly, the idea is not that the patients will actually experience aversive symptoms, and because of them
Ondansetron
The introduction of SSRIs and realization of their broad therapeutic spectrum, together with the isolation of serotonergic receptors greatly increased serotonin research during the late 1980s and early 1990s. During this era, it was expected that compounds targeting various components of central 5HT systems would also be evaluated for their ability to affect EtOH drinking. Early studies indicated that SSRIs and the 5HT3 antagonist ondansetron both suppressed various parameters of EtOH drinking
Animal models for target discovery and validation
First and second wave pharmacological treatments for alcoholism were defined as having demonstrated efficacy in humans in some fashion. It is more challenging to identify a third wave of compounds predicted to be effective in humans. Many animal paradigms in current use model various characteristics of alcoholism, but we are only beginning to use them effectively to differentiate clinically effective from clinically ineffective compounds (Egli, 2005, Heilig & Egli, 2005). How, then, are we to
Conclusion
Lessons learned from each wave of compounds will facilitate the development of additional medications. To be successfully marketed and widely prescribed in appropriate patients, first wave compounds will need to overcome multiple barriers such as lack of patient awareness and misperceptions concerning efficacy and side effects. Once these obstacles are overcome, it will be easier to navigate these potential barriers more efficiently as second wave target compounds become available. In addition,
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