J-113397

J-113397 is the first potent and selective nonpeptidyl ORL1 receptor antagonist (Ki: cloned human ORL1=1.8 nM) without any agonistic effects on other opioid receptors[1].

Signaling Pathways >> GPCR/G Protein >> Opioid Receptor

Signaling Pathways >> Neuronal Signaling >> Opioid Receptor

Research Areas >> Neurological Disease

NOP Receptor/ORL1:1.8 ± 0.24 nM (Ki)

κ Opioid Receptor/KOR:640 ± 87 nM (Ki)

μ Opioid Receptor/MOR:1000 ± 160 nM (Ki)

δ Opioid Receptor/DOR:>10000 nM (Ki)

J-113397 (0-500 nM) inhibits NociceptinNociceptin/orphanin FQ (HY-P0183)-stimulated [35S]GTPγS binding to CHO cells expressing ORL1 (CHO-ORL1) but had no effect on [35S]GTPγS binding by itself[1]. Cell Viability Assay[1] Cell Line: CHO-ORL1 cells Concentration: 0, 0.1, 1, 10, 100, 200, 500 nM Incubation Time: 10 min Result: Inhibited nociceptin/orphanin FQ-stimulated [35S]guanosine 5′-O-(γ-thio)triphosphate (GTPγS) binding to Chinese Hamster Ovary (CHO) cells expressing ORL1 (CHO-ORL1) with an IC50 value of 5.3 nM but had no effect on [35S]GTPγS binding by itself.

J-113397 (0-30 mg/kg; subcutaneously (s.c.); once) dose-dependently inhibits hyperalgesia elicited by intracerebroventricular (i.c.v.) administration of NociceptinNociceptin/orphanin FQ (HY-P0183) in a tail-flick test with mice[1]. Animal Model: Male ICR mice (15–25 g)[1] Dosage: 0, 3, 10, 30 mg/kg Administration: Subcutaneously (s.c.), 10 min prior to administering 0.1 nmol nociceptin/orphanin FQ to the mice Result: Dose-dependently inhibited hyperalgesia elicited by intracerebroventricular (i.c.v.) administration of nociceptin/orphanin FQ in a tail-flick test with mice.

[1]. Ozaki S, et al. In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist. Eur J Pharmacol. 2000 Aug 18;402(1-2):45-53.