Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction.
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.
Sneyd
J R
JR
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
Langton
J A
JA
Allan
L G
LG
Peacock
J E
JE
Rowbotham
D J
DJ
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*
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