title: Isobolographic analysis of epinephrine with bupivacaine, dextromethorphan, 3-methoxymorphinan, or dextrorphan on infiltrative anesthesia in rats: dose-response studies.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physical Therapy, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Liu
authors.forename: Jhi-Joung
authors.initials: JJ
authors.lastname: Wang
authors.forename: Willy
authors.initials: W
authors.lastname: Chou
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
mesh_terms: D000772:Anesthesia, Local / Q000379:methods; D019162:Anesthetics, Combined / Q000494:pharmacology; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D003915:Dextromethorphan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003917:Dextrorphan / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D023421:Models, Animal; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019162:Anesthetics, Combined; D000779:Anesthetics, Local; D018691:Excitatory Amino Acid Antagonists; D003917:Dextrorphan; C028657:3-methoxymorphinan; D003915:Dextromethorphan; D002045:Bupivacaine; D004837:Epinephrine