Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction.

J R Sneyd, J A Langton, L G Allan, J E Peacock, D J Rowbotham

Index: Br. J. Anaesth. 98(5) , 672-6, (2007)

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Abstract

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.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.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.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.