Sustained analgesic effect of the Rho kinase inhibitor AS1892802 in rat models of chronic pain

J Pharmacol Sci. 2010;114(1):119-22. doi: 10.1254/jphs.10158sc. Epub 2010 Aug 11.

Abstract

To assess the pharmacological profile of AS1892802, a novel and selective Rho kinase (ROCK) inhibitor, we examined the effects of repeated dosing with AS1892802 on models of monoiodoacetate-induced arthritis and streptozotocin-induced neuropathy. Although single dosing of AS1892802 exerted a short-acting, moderate analgesic effect, repeated dosing exhibited a long-lasting and more potent analgesic effect in both models. Furthermore, the analgesic effect was sustained for seven days after the last administration. These results suggest that peripheral ROCK plays a crucial role in chronic pain maintenance and that AS1892802 may be useful in treating chronic pain.

Publication types

  • Comparative Study

MeSH terms

  • Analgesics / administration & dosage
  • Animals
  • Chronic Disease
  • Delayed-Action Preparations
  • Disease Models, Animal*
  • Male
  • Pain / drug therapy*
  • Pain / enzymology
  • Pain Measurement / drug effects*
  • Pain Measurement / methods
  • Phenylurea Compounds / administration & dosage*
  • Pyridines / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • 1-(2-hydroxy-1-phenylethyl)-3-(4-(pyridin-4-yl)phenyl)urea
  • Analgesics
  • Delayed-Action Preparations
  • Phenylurea Compounds
  • Pyridines
  • rho-Associated Kinases