Effect of the low-affinity,noncompetitive N-methyl-d-aspartate receptor antagonist dextromethorphan on visceral perception in healthy volunteers

BACKGROUND: The use of N-methyl-d-aspartate (NMDA) receptor antagonists may hold promise for the treatment of pain of visceral origin, in particular in conditions characterized by visceral hypersensitivity. AIM: To study the effect of dextromethorphan, a low affinity, non-competitive NMDA receptor antagonist, on visceral perception in healthy volunteers. METHODS: Nine healthy volunteers (5 female, median age 22 years) underwent a gastric barostat study after oral administration of placebo, dextromethorphan 10 mg or dextromethorphan 30 mg, on three separate days in a double-blind, randomised order. Sensations induced by step-wise isobaric gastric distension (2 mmHg/2 min) were studied during fasting and 30 min after a meal. In addition, proximal gastric tone was measured during fasting and postprandially. RESULTS: Compared to placebo, dextromethorphan 30 mg significantly increased the distension-evoked sensation scores for nausea (P=0.004) and satiation (P=0.004) during fasting; and for bloating (P= 0.001), nausea (P=0.000) and satiation (P=0.01) 30 min postprandially. Dextromethorphan did not alter pain scores, proximal gastric tone or gastric compliance. CONCLUSIONS: Dextromethorphan increases the perception of non-painful sensations during gastric distension, without altering the perception of pain. Therefore, application of dextromethorphan as a visceral analgesic is questionable. Future studies with more specific NMDA receptor antagonist are warranted.