Comparison of ketamine and dextromethorphan in potentiating the antinociceptive effect of morphine in rats.
We compared the efficacy of two clinically available drugs with N-methyl-D-aspartate receptor antagonist properties, dextromethorphan and ketamine, in potentiating morphine-induced antinociception. Ketamine alone at 0.3-3 mg/kg had no effect on the hot plate test and at 10 mg/kg caused sedation/motor deficits. The antinociceptive effect of 5 mg/kg morphine was slightly enhanced by 1 mg/kg, but not 0.3 or 3 mg/kg, ketamine. Dextromethorphan alone at 45 mg/kg had no effect, but at 60 mg/kg caused sedation/motor deficit. At 15-45 mg/kg, dextromethorphan significantly and dose-dependently increased the magnitude and duration of morphine-induced antinociception. Dextromethorphan also potentiated morphine at doses that, by themselves, did not cause antinociception (1-2 mg/kg).


CONCLUSIONS
Dextromethorphan was more effective than ketamine in potentiating morphine-induced antinociception. Dextromethorphan may thus be the drug of choice for testing the interactions between N-methyl-D-aspartate antagonists and morphine clinically.
Plesan
A
A
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden. zsuzsanna.wiesenfeld-hallin@neurophys.hs.sll.se
Hedman
U
U
Xu
X J
XJ
Wiesenfeld-Hallin
Z
Z
D000698:Analgesia; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness / Q000187:drug effects; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects; D013997:Time Factors
D000700:Analgesics; D000701:Analgesics, Opioid; D000778:Anesthetics, Dissociative; D000996:Antitussive Agents; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D003915:Dextromethorphan; D009020:Morphine