A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397

被引：62

作者：

Ozaki, S ^{[1
]}

Kawamoto, H ^{[1
]}

Itoh, Y ^{[1
]}

Miyaji, M ^{[1
]}

Iwasawa, Y ^{[1
]}

Ohta, H ^{[1
]}

机构：

[1] Banyu Pharmaceut Co Ltd, Merck Res Labs, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2000年 / 387卷 / 03期

关键词：

nociceptin/orphanin FQ; ORL1; receptor; opioid;

D O I：

10.1016/S0014-2999(99)00822-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 [I-125][Tyr(14)]nociceptin binding to Chinese hamster ovary (CHO) cells expressing ORL1 receptor in a dose-dependent manner (IC50; 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 IC50 value of 26 nM. These results indicate that J-113397 is a potent and selective nonpeptidyl antagonist of the ORL1 receptor. (C) 2000 Elsevier Science B.V. All rights reserved.

引用

页码：R17 / R18

页数：2

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