A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397.
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.
Ozaki
S
S
Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Banyu Pharmaceutical, 3 Okubo, Tsukuba, Japan. ozakiss@banyu.co.jp
Kawamoto
H
H
Itoh
Y
Y
Miyaji
M
M
Iwasawa
Y
Y
Ohta
H
H
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D016466:CHO Cells; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D009292:Narcotic Antagonists; D010880:Piperidines / Q000494:pharmacology*; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor
D001562:Benzimidazoles; C402921:J 113397; D009292:Narcotic Antagonists; D010880:Piperidines; D011957:Receptors, Opioid; D005576:Colforsin; D000242:Cyclic AMP; D000094942:Nociceptin Receptor