[Dextromethorphan enhances analgesic activity of propacetamol--experimental study].
While many pre-clinical and clinical studies have suggested that the addition of N-methyl-d--aspartate (NMDA) receptor antagonists, such as dextromethorphan, to opioid analgesics, such as morphine may enhance the analgesic effects. The aim of the study was to assess the effect of non-competitive NMDA antagonists and paracetamol (propacetamol) on pain threshold and analgesic potency of this drugs and their combinations in formalin model for pain in rats. Intraperitoneal administration of paracetamol only in doses of 100 g/kg or higher resulted in increase of pain threshold in tail flick and paw pressure tests. The results of our study suggest that there was no significant difference in pain threshold between separate administration of dextromethorphan and in combination with paracetamol. In a formalin model for pain we have shown that paracetamol in non-analgesic doses (10 mg/kg) administered in combination with dextrometorphan, ketamine and mamantine was more effective than those drugs given separately but the best analgesic effect was obtained when combination of paracetamol and dextromethorphan was applied. The addition of higher doses of these combined drugs, that is paracetamol and all three NMDA antagonists did not result in enhancement of dose-dependant analgesia. In conclusion it should be stated that NMDA antagonists improve analgesic effect of paracetamol in the formalin model for pain. although only to a limited extend.
Dobrogowski
Jan
J
Zakład Badania i Leczenia Bólu, Katedra Anestezjologii, Collegium Medicum Uniwersytetu Jagiellońskiego.
Wordliczek
Jerzy
J
Przewłocka
Barbara
B
D000082:Acetaminophen / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003915:Dextromethorphan / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; C063776:propacetamol; D007649:Ketamine; D003915:Dextromethorphan