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.

CONCLUSION:

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: J R Sneyd, J A Langton, L G Allan, J E Peacock, D J Rowbotham
• Journal: British journal of anaesthesia (Br J Anaesth) Vol. 98 Issue 5 Pg. 672-6 (May 2007) ISSN: 0007-0912 [Print] England
• PMID: 17416906 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Non-Narcotic
• Anti-Inflammatory Agents, Non-Steroidal
• Purinergic P1 Receptor Agonists
• Diclofenac
• Adenosine
• N-((1S,trans)-2-hydroxycyclopentyl)adenosine

Topics

• Adenosine (administration & dosage, analogs & derivatives, therapeutic use)
• Adolescent
• Adult
• Analgesics, Non-Narcotic (administration & dosage, therapeutic use)
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Diclofenac (therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Molar, Third (surgery)
• Pain Measurement (methods)
• Pain, Postoperative (drug therapy, etiology)
• Purinergic P1 Receptor Agonists
• Tooth Extraction (adverse effects)