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

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.

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • CHO Cells
  • Colforsin / pharmacology
  • Cricetinae
  • Cyclic AMP / biosynthesis
  • Dose-Response Relationship, Drug
  • Narcotic Antagonists*
  • Nociceptin Receptor
  • Piperidines / pharmacology*
  • Receptors, Opioid


  • Benzimidazoles
  • J 113397
  • Narcotic Antagonists
  • Piperidines
  • Receptors, Opioid
  • Colforsin
  • Cyclic AMP
  • Nociceptin Receptor