title: The characteristics of intravenous adenosine-induced antinociception in a rabbit model of acute nociceptive pain: a comparative study with remifentanil.
abstract: BACKGROUND
  Adenosine and remifentanil are potent IV analgesics with ultrashort half-lives. The antinociceptive effect of IV adenosine has not been clearly characterized. We compared the antinociceptive effects of adenosine and remifentanil in rabbits.
  
  
  METHODS
  Sixteen rabbits, placed on a sling allowing reasonably free movement, received IV adenosine (400 microg x kg(-1) x min(-1)) or remifentanil (0.4 microg x kg(-1) x min(-1)) over 240 min.
  
  
  RESULTS
  Both drugs produced profound antinociception, as assessed by the number of animals unresponsive to clamping the forepaw and the electrical stimulation threshold of escape movement. With remifentanil, the antinociceptive effect increased rapidly, reaching its peak at 60 min, and then began to decline despite continued infusion. After stopping the infusion, it decreased rapidly and disappeared within 30 min. The vasodilating effect of IV adenosine was immediate in onset and ultrashort in duration. The antinociceptive effect of adenosine increased slowly but progressively during the infusion, reaching its peak only when the infusion ended. Then it decreased slowly over the following 360 min after terminating the infusion.
  
  
  CONCLUSIONS
  Remifentanil had a rapid onset and short duration of action, and probably showed signs of tolerance development, whereas the antinocieptive effect of adenosine was slow in onset and long-lasting, despite its ultrashort plasma half-life and the immediate on-off profiles of its vasodilating effect.
authors.affiliation: Surgical Center, Research Hospital, Institute of Medical Institute, The University of Tokyo, Tokyo, Japan. hayashida-todai@umin.ac.jp
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hayashida
authors.forename: Atsuo
authors.initials: A
authors.lastname: Fukunaga
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakurai
authors.forename: Hideki
authors.initials: H
authors.lastname: Mamiya
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ichinohe
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hanaoka
mesh_terms: D000241:Adenosine / Q000493:pharmacokinetics / Q000494:pharmacology*; D000700:Analgesics / Q000493:pharmacokinetics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D000077208:Remifentanil; D012119:Respiration / Q000187:drug effects
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D018685:Anesthetics, Inhalation; D010880:Piperidines; D002245:Carbon Dioxide; D007530:Isoflurane; D000241:Adenosine; D000077208:Remifentanil