title: Interaction between sufentanil and U-50488H with respect to antinociception and respiratory depression in rats.
abstract: BACKGROUND
  Opiate receptors have been argued to differentially regulate analgesia and respiratory depression. In order to validate possible interactions between the opiate mu- and kappa-receptors, interactions between sufentanil and U-50488H were studied in rats.
  
  
  METHODS
  Rats equipped with an arterial catheter were tested in the tail flick latency (TFL) test after intravenous treatment with sulentanil (a mu-agonist), U-50488H (a kappa-agonist) or fixed ratio combinations of both drugs. Simultaneously, respiratory changes were monitored by blood gas analysis.
  
  
  RESULTS
  The ED50s of sufentanil for a TFL > 6.0 and > or = 10.0 s were 0.0002 and 0.00059 mg/kg. For U-50488H the corresponding values were 1.53 and 8.11 mg/kg. Using a fixed dose ratio of 1/10,000, an additivity was demonstrated between sufentanil and U-50488H in terms of antinociception. With regard to respiratory parameters, PaCO2 significantly increased after all doses of sufentanil early after treatment. At the higher doses tested, there was also a decrease in PaO2 and O2 saturation. For U-50488H only the highest doses resulted in an early and small shift in PaCO2. The combination of sufentanil/U-50488H resulted in only a small increase in PaCO2 at the highest dose regimen tested.
  
  
  CONCLUSIONS
  The results presented here demonstrate that drug mixtures of sufentanil and U-50488H can be additive with respect to antinociception with additionally less risk for respiratory side-effects, as compared with sufentanil alone. Therefore, a combination of mu- and kappa-opiate-receptor agonists might be more beneficial than each agent alone.
authors.affiliation: Department of Anesthesia, University Hospital, Free University Brussels, Belgium.
authors.forename: C M
authors.initials: CM
authors.lastname: Verborgh
authors.forename: F
authors.initials: F
authors.lastname: Camu
authors.forename: T F
authors.initials: TF
authors.lastname: Meert
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004357:Drug Synergism; D008297:Male; D010100:Oxygen / Q000097:blood; D011759:Pyrrolidines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000503:physiopathology; D017409:Sufentanil / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D002245:Carbon Dioxide; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D017409:Sufentanil; D010100:Oxygen