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Overview
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Background
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].
[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.
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