title: Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction.
abstract: BACKGROUND
  Adenosine is analgesic in humans, and the selective adenosine A1 receptor agonist GR79236X has significant anti-nociceptive activity in an animal pain model of inflammatory pain.
  
  
  METHODS
  Seventy-nine patients with moderate pain after third molar extraction under general anaesthesia were randomized to receive a 15 min double-blind infusion containing either GR79236X 4 microg kg-1, GR79236X 10 microg kg-1, diclofenac 50 mg, or saline placebo. Rescue analgesia was promptly available to all patients.
  
  
  RESULTS
  Meaningful pain relief (mild or no pain) was attained by 9 (47%) patients in the placebo group, 12 (63%) patients in the GR79236 4 microg kg-1 group, 10 (48%) patients in the 10 microg kg-1 group, and 16 (80%) patients in the diclofenac 50 mg group. Neither dose of GR79236 produced a significant improvement over placebo, but diclofenac was superior to both placebo (P=0.036) and GR79236 10 microg kg-1 (P=0.034). Median times to rescue or additional analgesia were 62, 100, 60, and 363 min for patients receiving placebo, GR79236 4 microg kg-1, 10 microg kg-1, and diclofenac 50 mg, respectively (diclofenac significantly longer than placebo, P=0.002 log-rank test). Pain control was poor in the placebo group and in both GR79236 groups, with between 79 and 86% of patients having good pain control (i.e. mild or no pain) for <20% of the time compared with only 30% of patients who received diclofenac.
  
  
  CONCLUSIONS
  We found no evidence of efficacy of GR79236 compared with placebo, but the active control diclofenac was effective. It is possible that a higher dose of GR79236 might have been effective or that i.v. administration of this drug does not achieve appropriate concentrations in the brain or peripheral nerves.
authors.affiliation: Anaesthesia Research Group, Peninsula Medical School, The John Bull Building, Tamar Science Park, Drake Circus, Plymouth PL6 8BU, and Department of Anaesthesia, Northwick Park Hospital, Harrow, UK. robert.sneyd@pms.ac.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Sneyd
authors.forename: J A
authors.initials: JA
authors.lastname: Langton
authors.forename: L G
authors.initials: LG
authors.lastname: Allan
authors.forename: J E
authors.initials: JE
authors.lastname: Peacock
authors.forename: D J
authors.initials: DJ
authors.lastname: Rowbotham
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D004008:Diclofenac / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008964:Molar, Third / Q000601:surgery*; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy* / Q000209:etiology; D058906:Purinergic P1 Receptor Agonists; D014081:Tooth Extraction / Q000009:adverse effects*
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D058906:Purinergic P1 Receptor Agonists; D004008:Diclofenac; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine