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Acamprosate in Alcohol Dependence: Implications of a Unique Mechanism of Action

Littleton, John M. MD, PhD

doi: 10.1097/ADM.0b013e318156c26f
Review Article

Acamprosate, in combination with psychosocial therapy, has been shown to be clinically effective in maintaining abstinence in alcohol dependence. Current research suggests that its mechanism of action involves functional antagonism of the ionotropic glutamate N-methyl-d-aspartate (NMDA) receptor. However, direct interactions between acamprosate and the NMDA receptor are weak, and recent findings suggest that acamprosate may modulate NMDA receptors via regulatory polyamine sites, or that it may act directly on metabotropic glutamate receptors. All of these mechanisms are novel for the treatment of alcohol dependence and have far-reaching implications for understanding relapse, as well as for the discovery of drugs with greater efficacy. Understanding the mechanism of action of acamprosate may be an important stimulus for change in the perception and treatment of alcohol dependence.

From the Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY.

Received June 21, 2007; revised July 24, 2007; accepted July 27, 2007.

Dr. Littleton is a consultant for Forest Laboratories, Inc. and has received research funds from Merck s.a. to investigate the mechanism of action of acamprosate.

Send correspondence and reprint requests to Dr. John M. Littleton, Department of Pharmaceutical Sciences, University of Kentucky, Kentucky Tobacco Research and Development Center, Cooper and University Drives, Lexington, KY 40546. e-mail:

© 2007 American Society of Addiction Medicine