Novel p38α mitogen-activated protein kinase inhibitor shows analgesic efficacy in acute postsurgical dental pain.

Abstract

SCIO-469 is a selective p38α mitogen-activated protein kinase (MAPK) inhibitor for preclinical models of acute pain. This prospective, double-blind, randomized clinical study compared efficacy and safety of oral SCIO-469, ibuprofen, and placebo in postsurgical dental pain. Subjects (n = 263) undergoing extraction of 1 or more impacted mandibular third molars received preoperative treatment with SCIO-469 (150, 210, or 300 mg), ibuprofen (400 mg), or placebo; the 210-mg group received 90 mg postoperatively. A 4-point categorical scale and a 100-mm visual analogue scale were used to measure pain intensity. The primary end point was median time from first incision to first rescue medication using the Kaplan-Meier product limit estimator. All SCIO-469 groups had significantly longer times to rescue medication compared with placebo; preoperative and postoperative treatment with 210 + 90 mg SCIO-469 resulted in 8.1 hours versus 4.1 hours to rescue for placebo (P = .003). Ibuprofen also increased time to rescue medication (6.6 hours) versus placebo (P = .04). Dizziness, headache, and nausea were the most frequently reported adverse events. This is the first clinical demonstration of antinociceptive effects in acute pain with preoperative administration of a p38α MAPK inhibitor.

• Authors: Sandra E Tong, Stephen E Daniels, Peter Black, Stephen Chang, Andrew Protter, Paul J Desjardins
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 52 Issue 5 Pg. 717-28 (May 2012) ISSN: 1552-4604 [Electronic] England
• PMID: 21659629 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Analgesics
• Indoles
• Protein Kinase Inhibitors
• SCIO-469
• Mitogen-Activated Protein Kinase 14
• Ibuprofen

Topics

• Acute Pain (diagnosis, enzymology, etiology, prevention & control)
• Administration, Oral
• Adolescent
• Adult
• Analgesics (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Ibuprofen (therapeutic use)
• Indoles (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Kaplan-Meier Estimate
• Male
• Mitogen-Activated Protein Kinase 14 (antagonists & inhibitors, metabolism)
• Molar, Third (surgery)
• Pain Measurement
• Prospective Studies
• Protein Kinase Inhibitors (adverse effects, pharmacokinetics, therapeutic use)
• Time Factors
• Tooth Extraction (adverse effects)
• Tooth, Impacted (surgery)
• Treatment Outcome
• United States
• Young Adult