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Aripiprazole: A Drug with a Novel Mechanism of Action and Possible Efficacy for Alcohol Dependence

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Abstract:

Alcohol dependence is a costly and socially devastating illness. The dopamine system has received increased attention due to the consensus that dopaminergic dysfunction is at the core of the addiction process. Agents that modulate this system might be beneficial in reducing craving, reward, and relapse. Aripiprazole is a 3rd generation atypical antipsychotic U.S. Food and Drug Administrationapproved for the treatment of schizophrenia, bipolar disorder, and treatment-resistant major depression. Its principal mechanism of action appears to be associated with partial agonism at the D2 dopamine receptor. Nevertheless, relatively recent pre-clinical data shows that aripiprazole might exert its action by way of agonism, partial agonism, and antagonism at both dopamine and serotonin receptors. In animal models of alcoholism aripiprazole produced an overall decrease in drinking behavior. Clinical trials with aripiprazole in alcoholics have shown some positive, but inconsistent, results. Given aripiprazole's putative activity on frontal-subcortical circuits subserving reward/craving and impulsive behavior, it might prove to be beneficial for neuropsychiatric conditions in which dysregulation of reward and impulsivity, among them alcoholism, are at the core of the syndrome. This article proposes a potential role for aripiprazole in alcoholism treatment, and suggests that more randomized controlled trials should be designed at appropriate doses to better understand aripiprazole's potential role as a treatment option. More options are needed to treat alcoholics that fall into different subgroups (e.g., those with impulsive disorders), or non-responsive to available treatments. Early results with aripiprazole are promising and warrant further exploration.





Keywords: Dopamine; alcoholism; dopamine receptor; partial agonist; treatment

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/187152710790966731

Publication date: March 1, 2010

More about this publication?
  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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