Isobolographic analysis of epinephrine with bupivacaine, dextromethorphan, 3-methoxymorphinan, or dextrorphan on infiltrative anesthesia in rats: dose-response studies

Reg Anesth Pain Med. 2008 Mar-Apr;33(2):115-21. doi: 10.1016/j.rapm.2007.08.012.

Abstract

Background and objectives: The aims of this study were to establish the potencies of epinephrine, bupivacaine, dextromethorphan, 3-methoxymorphinan, and dextrorphan and evaluate interactions of epinephrine with bupivacaine, dextromethorphan, 3-methoxymorphinan, or dextrorphan as an infiltrative anesthetic. Bupivacaine, a common and long-acting local anesthetic, was used as control.

Methods: Dose-dependent responses of epinephrine, dextromethorphan, 3-methoxymorphinan, and dextrorphan on cutaneous analgesia were compared with bupivacaine in rats. The interactions of drugs were evaluated via an isobolographic analysis.

Results: We found that epinephrine, bupivacaine, dextromethorphan, 3-methoxymorphinan, and dextrorphan produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. Relative potencies were epinephrine > bupivacaine > dextromethorphan > 3-methoxymorphinan > dextrorphan (P < .01 for each comparison). Coadministration of bupivacaine with epinephrine produced a synergistic effect, and coadministration of dextromethorphan, 3-methoxymorphinan, or dextrorphan with epinephrine produced an additive effect.

Conclusions: Epinephrine, dextromethorphan, 3-methoxymorphinan, and dextrorphan are known to have local anesthetic effects as infiltrative cutaneous analgesia in rats. Epinephrine increased the potency of bupivacaine, but not dextromethorphan, 3-methoxymorphinan, or dextrorphan as an infiltrative anesthetic. The cutaneous analgesic effects of adding epinephrine to dextromethorphan, 3-methoxymorphinan, or dextrorphan, are similar to combinations of 2 local anesthetics.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, Local / methods
  • Anesthetics, Combined / pharmacology
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / pharmacology*
  • Animals
  • Bupivacaine / administration & dosage
  • Bupivacaine / pharmacology*
  • Dextromethorphan / administration & dosage
  • Dextromethorphan / analogs & derivatives*
  • Dextromethorphan / pharmacology*
  • Dextrorphan / administration & dosage
  • Dextrorphan / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Epinephrine / administration & dosage
  • Epinephrine / pharmacology*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Injections, Subcutaneous
  • Male
  • Models, Animal
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anesthetics, Combined
  • Anesthetics, Local
  • Excitatory Amino Acid Antagonists
  • Dextrorphan
  • 3-methoxymorphinan
  • Dextromethorphan
  • Bupivacaine
  • Epinephrine