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.


OBJECTIVE
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.
Kuiken
S D
SD
Department of Gastroenterology and Heptalogy, Academic Medical Centre, Amsterdam, the Netherlands.
Lei
A
A
Tytgat
G N J
GN
Holman
R
R
Boeckxstaens
G E E
GE
D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D003915:Dextromethorphan / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004415:Dyspepsia / Q000209:etiology / Q000517:prevention & control*; D005215:Fasting; D005260:Female; D013271:Gastric Dilatation; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D019518:Postprandial Period; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013270:Stomach / Q000187:drug effects*
D000701:Analgesics, Opioid; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan