Sustained analgesic effect of the Rho kinase inhibitor AS1892802 in rat models of chronic pain.
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.
Yoshimi
Eiji
E
Pharmacology Research Laboratories, Astellas Pharma Inc., Japan. eiji.yoshimi@jp.astellas.com
Yamamoto
Hiroko
H
Furuichi
Yasuhisa
Y
Shimizu
Yasuaki
Y
Takeshita
Nobuaki
N
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D002908:Chronic Disease; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000201:enzymology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C552258:1-(2-hydroxy-1-phenylethyl)-3-(4-(pyridin-4-yl)phenyl)urea; D000700:Analgesics; D003692:Delayed-Action Preparations; D010671:Phenylurea Compounds; D011725:Pyridines; D054460:rho-Associated Kinases