In a recent article, Krystal et al1 demonstrated dose-dependent ethanol-like effects in detoxified alcoholic patients induced by ketamine, a high-affinity noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Alcohol has repeatedly been shown to have NMDA antagonistic effects2; however, whether it resembles high-affinity or low-affinity NMDA is not clear. Preclinical drug discrimination studies have shown dextromethorphan, a low-affinity noncompetitive NMDA antagonist, to have effects that overlap with, but do not fully resemble, ketamine.3 Like ketamine, dextromethorphan is not a pure NMDA antagonist, especially since σ binding has been reported.4 The properties of σ receptors and nonopioid non-NMDA receptors are not well understood.
Alcohol Sensation Score in alcoholic patients and controls after challenge with dextromethorphan, 2 mg/kg.
Time until dextromethorphan induced craving for alcohol, as measured by the visual analog scale.
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