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

• Published in: British journal of anaesthesia : BJA Vol. 98; no. 5; pp. 672 - 676
• Main Authors: Sneyd, J.R., Langton, J.A., Allan, L.G., Peacock, J.E., Rowbotham, D.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2007; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: acute; acute pain; acute pain, novel techniques; Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - therapeutic use; Adolescent; Adult; anaesthesia; anaesthesia, dental; analgesics non-opioid; analgesics non-opioid, diclofenac; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - therapeutic use; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; dental; diclofenac; Diclofenac - therapeutic use; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Medical sciences; Middle Aged; Molar, Third - surgery; novel techniques; pain; Pain Measurement - methods; pain, acute; Pain, Postoperative - drug therapy; Pain, Postoperative - etiology; Purinergic P1 Receptor Agonists; Tooth Extraction - adverse effects; analgesics non-opioid, diclofenac; pain, acute; acute pain, novel techniques; anaesthesia, dental; Human; Prostaglandin-endoperoxide synthase; acute; Purine nucleoside; Adenosine; novel techniques; anaesthesia; Enzyme; acute pain; diclofenac; pain; Enzyme inhibitor; dental; analgesics non-opioid; Diclofenac; Non steroidal antiinflammatory agent; Arylacetic acid derivatives; Analgesic; Pain; Antipyretic; Anesthesia; Oxidoreductases
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/aem075

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 µg kg −1, GR79236X 10 µg 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 µg kg −1 group, 10 (48%) patients in the 10 µg 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 µg 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 µg kg −1, 10 µg 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.