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NMDA Receptor Modulators in the Treatment of Drug Addiction
Department of Psychology, Arizona State University, Tempe, AZ 85287, USA
Interdisciplinary Graduate Program in Neuroscience, Arizona State University, Tempe, AZ 85287, USA
* Author to whom correspondence should be addressed.
Received: 30 November 2012; in revised form: 29 January 2013 / Accepted: 29 January 2013 / Published: 6 February 2013
Abstract: Glutamate plays a pivotal role in drug addiction, and the N-methyl-D-aspartate (NMDA) glutamate receptor subtype serves as a molecular target for several drugs of abuse. In this review, we will provide an overview of NMDA receptor structure and function, followed by a review of the mechanism of action, clinical efficacy, and side effect profile of NMDA receptor ligands that are currently in use or being explored for the treatment of drug addiction. These ligands include the NMDA receptor modulators memantine and acamprosate, as well as the partial NMDA agonist D-cycloserine. Data collected to date suggest that direct NMDA receptor modulators have relatively limited efficacy in the treatment of drug addiction, and that partial agonism of NMDA receptors may have some efficacy with regards to extinction learning during cue exposure therapy. However, the lack of consistency in results to date clearly indicates that additional studies are needed, as are studies examining novel ligands with indirect mechanisms for altering NMDA receptor function.
Keywords: glutamate; N-methyl-D-aspartate receptor; glycine binding site; antagonist; partial agonist
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Tomek, S.E.; Lacrosse, A.L.; Nemirovsky, N.E.; Olive, M.F. NMDA Receptor Modulators in the Treatment of Drug Addiction. Pharmaceuticals 2013, 6, 251-268.
Tomek SE, Lacrosse AL, Nemirovsky NE, Olive MF. NMDA Receptor Modulators in the Treatment of Drug Addiction. Pharmaceuticals. 2013; 6(2):251-268.
Tomek, Seven E.; Lacrosse, Amber L.; Nemirovsky, Natali E.; Olive, M. F. 2013. "NMDA Receptor Modulators in the Treatment of Drug Addiction." Pharmaceuticals 6, no. 2: 251-268.