title: The N-methyl-D-aspartate-receptor antagonist dextromethorphan lacks analgesic effect in a human experimental ischemic pain model.
abstract: BACKGROUND
  N-methyl-D-aspartate-receptor antagonists may be useful in pain management. The aim of this study was to evaluate dextromethorphan (DEX), a commonly used oral antitussive drug with NMDA-receptor antagonistic properties, in respect of its analgesic properties as single drug and co-administered with morphine (MO) on experimental ischemic pain. In addition, the analgesic effects of another clinically available NMDA-receptor antagonist, ketamine (KET) as well as of morphine (MO) were tested as active controls.
  
  
  METHODS
  Nineteen healthy volunteers were included in the study. Experimental ischemic pain was induced using the forearm tourniquet test. Placebo (PLAC), oral DEX (30 and 90 mg, respectively), KET (9 microg kg(-1) min(-1) i.v.), MO (0.1 mg kg(-1), i.v.) and the DEX+MO and KET+MO combinations were evaluated during eight separate experiments. Development of ischemic pain was rated by visual analog scale (VAS) every minute over 30 min and ratings were summed as sum of pain scores (SPS).
  
  
  RESULTS
  DEX by itself did not influence SPS compared to PLAC. The DEX+MO co-administration did not enhance MO-induced analgesia. MO and KET reduced pain ratings by 27% and 39%, respectively. The KET+MO combination showed no enhancement of the analgesic effect in comparison with the respective drugs in monotherapy.
  
  
  CONCLUSIONS
  DEX in clinical doses has no effect on the present acute ischemic pain model and does not influence MO-induced analgesia. Further studies on other pain modalities are needed in order to evaluate the potential use of DEX in pain treatment.
authors.affiliation: Karolinska Institutet, Department of Medical Laboratory Sciences and Technology, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Plesan
authors.forename: A
authors.initials: A
authors.lastname: Sollevi
authors.forename: M
authors.initials: M
authors.lastname: Segerdahl
mesh_terms: D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use; D003915:Dextromethorphan / Q000009:adverse effects / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007511:Ischemia; D007551:Isotonic Contraction / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004338:Drug Combinations; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D009020:Morphine