Biological Activity
(±)-j 113397 is a potent and selective non-peptidyl antagonist of orl1 receptor, with a ki value of 1.8 nm for cloned human orl1 [1].the orl1 receptor is a g protein-coupled. it is structurally related to the opioid receptors. the heptadecapeptide nociceptin/orphanin fq is the endogenous ligand [2].in cho-orl1 cells, nociceptinr/orphanin fq dose-dependently suppressed the accumulation of cyclic amp stimulated by forskolin with an ec value of 0.22 ± 0.011 nm. treatment with j-113397 at increasing concentration shifted the concentration-response curve of nociceptinr/orphanin fq to the right. data indicated that j-113397 inhibited the interaction between nociceptinr/orphanin fq and orl1 in a competitive manner [1].in a tail-flick test, an i.c.v. injection of nociceptinr/orphanin fq at 0.01-1 nmol or saline was given to mice. i.c.v. injection of saline did not obviously change the latency of tail-flick. nociceptinr/orphanin fq at doses of more than 0.1 nmol shortened the latency. at the high concentration, the effect of nociceptinr/orphanin fq reached a maximal decrease at 15 min after the injection of j-113397. the effect of nociceptinr/orphanin fq lasted for more than 60 min. j-113397 inhibited the shortening of mouse tail-flick latency induced by nociceptinr/orphanin fq dose-dependently. j-113397 at 30 mg/kg completely reversed the hyperalgesia elicited by nociceptinr/orphanin fq [1].
References
[1]. ozaki s, kawamoto h, itoh y, et al. in vitro and in vivo pharmacological characterization of j-113397, a potent and selective non-peptidyl orl1 receptor antagonist. european journal of pharmacology, 2000, 402(1): 45-53.
[2]. mollereau c, mouledous l. tissue distribution of the opioid receptor-like (orl1) receptor. peptides, 2000, 21(7): 907-917.
![(±)-1-[(3R*,4R*)-1-(Cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one Structure](https://www.chemicalbook.com/CAS/20200611/GIF/217461-40-0.gif)