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Isobolographic Analysis of Epinephrine With Bupivacaine, Dextromethorphan, 3-Methoxymorphinan, or Dextrorphan on Infiltrative Anesthesia in Rats: Dose-Response Studies
  1. Yu-Wen Chen, Ph.D.a,b,
  2. Kuo-Sheng Liu, Ph.D.d,
  3. Jhi-Joung Wang, M.D., Ph.D.b,
  4. Willy Chou, M.D.c and
  5. Ching-Hsia Hung, Ph.D.e
  1. aDepartment of Physical Therapy, China Medical University, Taichung, Taiwan
  2. bDepartment of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan
  3. cDepartment of Rehabilitation Medicine, Chi-Mei Medical Center, Tainan, Taiwan
  4. dGraduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
  5. eDepartment of Physical Therapy, National Cheng Kung University, Tainan, Taiwan.

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.

  • Epinephrine
  • Cutaneous analgesia
  • Bupivacaine
  • Dextromethorphan
  • 3-Methoxymorphinan
  • Dextrorphan
  • Local anesthetics
  • Isobolographic analysis

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Footnotes

  • Reprint requests: Ching-Hsia Hung, Ph.D., Department of Physical Therapy, National Cheng Kung University, No.1 Ta-Hsueh Road, Tainan, Taiwan. E-mail: chhung{at}mail.ncku.edu.tw

  • The authors gratefully acknowledge the financial support provided for this study by the National Science Council (NSC 94-2314-B-006-030 and NSC 96-2314-B-039-026) of Taiwan. This work was done at the National Cheng Kung University Medical College, Tainan, Taiwan.

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