Background:

(±)-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].

参考文献:
[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.