Analgesic efficacy of the kappa-receptor agonist, enadoline, in dental surgery pain

Clin Neuropharmacol. 1996 Feb;19(1):92-7. doi: 10.1097/00002826-199619010-00009.


To study the analgesic efficacy of enadoline, a selective agonist of the kappa-opioid receptor, a double-blind, randomized comparison was made of enadoline versus placebo and a combination of acetaminophen-codeine in patients with pain after surgical extraction of impacted molar teeth. An initial study involving a comparison of enadoline, a combination, and placebo failed to show any analgesic effect of enadoline. Therefore, a second study with the same design but using higher doses of enadoline was conducted. Despite continued safety and tolerability even at the higher doses, enadoline could not be shown to be superior to placebo. The acetaminophen-codeine combination was significantly more effective than enadoline or placebo. Enadoline did not show analgesic efficacy in this study. Possible reasons for this lack of efficacy are discussed.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / therapeutic use
  • Adult
  • Analgesics, Non-Narcotic / therapeutic use
  • Analgesics, Opioid / therapeutic use
  • Benzofurans / administration & dosage
  • Benzofurans / adverse effects
  • Benzofurans / therapeutic use*
  • Codeine / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Humans
  • Male
  • Molar, Third
  • Pain, Postoperative / drug therapy*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use*
  • Receptors, Opioid, kappa / agonists*
  • Tooth Extraction*


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Benzofurans
  • Drug Combinations
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • Acetaminophen
  • enadoline
  • Codeine