Seltorexant, also known as JNJ-42847922 and MIN-202, is a potent OX2R antagonist that has been shown to promote sleep in various species. JNJ-42847922 had an approximate 2-log selectivity ratio versus the human orexin-1 receptor. Ex vivo receptor binding studies demonstrated that JNJ-42847922 quickly occupied OX2R binding sites in the rat brain after oral administration and rapidly cleared from the brain. Seltorexant shows antidepressant and sleep-promoting effects in patients with major depressive disorder. JNJ-42847922 induces somnolence in healthy subjects without residual central effects.
Seltorexant (JNJ-42847922) is an orally active, high-affinity, and selective orexin-2 receptor (OX2R) antagonist (pKi values of 8.0 and 8.1 for human and rat OX2R). Seltorexant (JNJ-42847922) crosses the blood-brain barrier and quickly occupies OX2R binding sites in the rat brain[1].
Seltorexant (JNJ-42847922) (3-30 mg/kg; p.o.) dose-dependently induces and prolongs sleep in male Sprague-Dawley rats[1].
The sleep-promoting effects of Seltorexant (30 mg/kg; p.o.; per day for 7 days) are maintained upon 7-day repeated dosing in rats[1].
| Animal Model: | Male Sprague-Dawley rats (350-450 g)[1] |
| Dosage: | 30 mg/kg |
| Administration: | p.o.; per day for 7 days |
| Result: | The reduced sleep onset (non–rapid eye movement (NREM) latency) and the increased NREM sleep duration were maintained upon 7-day repeated dosing with JNJ-42847922. The prolongation of NREM sleep time was due to a significant increase in NREM bout duration throughout the treatment period assessed on D1 and D7. Rapid eye movement (REM) sleep was only marginally affected on D4 of treatment, resulting in a small but significant reduction in REM sleep latency and an increase in REM sleep duration. |
human OX2R: 8.0 (pKi); rat OX2R: 8.1 (pKi)
[1] Bonaventure P, et al. Characterization of JNJ-42847922, a Selective Orexin-2 Receptor Antagonist, as a Clinical Candidate for the Treatment of Insomnia. J Pharmacol Exp Ther. 2015 Sep;354(3):471-82. DOI:
10.1124/jpet.115.225466
