(R)-JNJ-31020028

(R)-JNJ-31020028 is a high affinity, selective brain penetrant neuropeptide Y Y2 receptor antagonist, with pIC50 values of 8.07, 8.22 and 8.21 for human, rat, and mouse Y2 receptor, respectively. (R)-JNJ-31020028 shows >100-fold selective versus human Y1, Y4, and Y5 receptors. (R)-JNJ-31020028 has antidepressant like effects[1][2].

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> Neuropeptide Y Receptor

human Y2 receptor:8.07 (pIC50)

rat Y2 receptor:8.22 (pIC50)

mouse Y2 receptor:8.21 (pIC50)

(R)-JNJ-31020028 (5.6 μg; chronic icv infusion; daily for 10 days) has antidepressant like effects in the olfactory bulbectomized rat (OBX) model[1]. Chronic icv administration of (R)-JNJ-31020028 at 5.6 μg/day using osmotic Alzet pump resulted in a significant decreases number of grooming events[1]. (R)-JNJ-31020028 treatment shows the Cmax, Tmax , AUCinf, Vd, and t1/2 were 4.35 μM, 0.5 hours, 7.91 h μM and 0.83 hours, respectively[1]. Animal Model: Male Sprague Dawley rats weighing 150-170 (OBX model)[1] Dosage: 5.6 μg Administration: chronic icv infusion; daily for 10 days Result: Reduced OBX rat immobility time. Animal Model: male Sprague-Dawley rat[2] Dosage: 10 mg/kg Administration: s.c. (Pharmacokinetic Analysis) Result: The Cmax, Tmax , AUCinf, Vd, and t1/2 were 4.35 μM, 0.5 hours, 7.91 h μM and 0.83 hours, respectively.

[1]. Shoblock JR, et al. In vitro and in vivo characterization of JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), a selective brain penetrant small molecule antagonist of the neuropeptide Y Y(2) receptor. Psychopharmacology (Berl). 2010 Feb;208(2):265-77.

[2]. Morales-Medina JC, et al. Chronic administration of the Y2 receptor antagonist, JNJ-31020028, induced anti-depressant like-behaviors in olfactory bulbectomized rat. Neuropeptides. 2012 Dec;46(6):329-34.