Biological Activity
ono-8130 is an orally bioavailable and selective antagonist of the prostaglandin e2 (pge2) receptor ep1 with ki value of 1.9 nm [1][2][3].prostaglandins contribute to the sensitization of peripheral and central nociceptive neurons during peripheral inflammation. prostaglandin e2 (pge2) is considered a dominant pronociceptive prostanoid. pge2 receptors are g protein-coupled receptors and classified into 4 general subtypes (ep1, ep2, ep3, and ep4) that are located unevenly in different tissues. ep1 receptors play a major role in processing of pain [1].in cystitis-related bladder pain mice, oral preadministration of ono-8130 at 0.3-30 mg/kg strongly prevented both the bladder pain-like behavior and referred hyperalgesia in a dose-dependent way. ono-8130 at 30 mg/kg also reversed the established cystitis-related bladder pain. ono-8130 also blocked prostaglandin e2 caused prompt phosphorylation of erk in the l6 spinal cord [1]. in the guinea pig trachea (gpt), ono-8130 inhibited the initial contraction mediated by pge2. ono-8130 also eliminated the spontaneous tone [2].
References
[1]. miki t, matsunami m, nakamura s, et al. ono-8130, a selective prostanoid ep1 receptor antagonist, relieves bladder pain in mice with cyclophosphamide-induced cystitis. pain. 2011 jun;152(6):1373-81.
[2]. sfholm j, dahlén se, adner m. antagonising ep1 and ep2 receptors reveal that the tp receptor mediates a component of antigen-induced contraction of the guinea pig trachea. eur j pharmacol. 2013 oct 15;718(1-3):277-82.
