一种强效且高度选择性的非肽类孤啡肽/孤啡肽FQ受体（ORL1）拮抗剂：J-113397。
A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397.
作者信息
Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Iwasawa Y, Ohta H
机构信息
Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Banyu Pharmaceutical, 3 Okubo, Tsukuba, Japan.
出版信息
Eur J Pharmacol. 2000 Jan 17;387(3):R17-8. doi: 10.1016/s0014-2999(99)00822-5.
We discovered a potent nociceptin/orphanin FQ receptor (ORL1) receptor antagonist, J-113397 (1-[(3R, 4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one). J-113397 inhibited [125I][Tyr(14)]nociceptin binding to Chinese hamster ovary (CHO) cells expressing ORL1 receptor in a dose-dependent manner (IC(50); 2. 3 nM), but showed 600-fold or less affinity for mu-, delta- and kappa-opioid receptors. Nociceptin/orphanin FQ-induced suppression of cyclic AMP accumulation elicited by forskolin was completely inhibited by J-113397 with an IC(50) value of 26 nM. These results indicate that J-113397 is a potent and selective nonpeptidyl antagonist of the ORL1 receptor.
我们发现了一种强效的孤啡肽/孤啡肽FQ受体（ORL1）拮抗剂J-113397（1-[(3R, 4R)-1-环辛基甲基-3-羟甲基-4-哌啶基]-3-乙基-1, 3-二氢-2H-苯并咪唑-2-酮）。J-113397以剂量依赖性方式抑制[125I][酪氨酸(14)]孤啡肽与表达ORL1受体的中国仓鼠卵巢（CHO）细胞的结合（IC(50)；2.3 nM），但对μ-、δ-和κ-阿片受体的亲和力低600倍或更低。J-113397以26 nM的IC(50)值完全抑制了孤啡肽/孤啡肽FQ诱导的由福司可林引起的环磷酸腺苷积累的抑制作用。这些结果表明J-113397是一种强效且选择性的ORL1受体非肽类拮抗剂。
Zotero 插件