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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 binding has been reported.⁴ The properties of receptors and nonopioid non-NMDA receptors are not well understood.

Dextromethorphan has been used as an over-the-counter antitussive medication for more than 40 years. Its safety profile is extremely favorable. Recently, it has received renewed interest as a medication with neuroprotective effects.⁵ Other areas of ongoing research include treatment of opioid-dependent patients and use as a tolerance-decreasing adjuvant medication in pain treatment.⁶ . . . [Full Text of this Article]